Spreadsheet: 0bdc995f-ce9b-4b39-9224-6810bb7aded4
Sheet: Relation Table

Relation | Type | Sentence | MedLine Reference | Connectivity | # of References | Owner | BiomarkerType
BCL2; PI3K; NF-kB; KDR; IL6; AKT1; EGFR; NFKBIA; DUSP1; ESR1; NOTCH1; [NAME]; gamma-secretase; PDPK1; [NAME]; ERBB4; HDAC1; ABCG2; PIP3 | Expression |  |  | 19 | 0
ICAM1 --+> MMP2 | Regulation | From correlation analysis ensues that the bond of ICAM-1 and VCAM-1 on chondrocytes with appropriate integrin ligands probably leads to up-regulation of gelatinase A and B and to down-regulation of TIMP-1., Similarly, the functional relationship between LFA-1/ICAM-1 and [NAME] may also explain the previously reported inability of purified ICAM-1 to induce MMP-2, and of purified VCAM-1 to induce [NAME] expression in T cells (14). | 12404960:8, 9510201:1225 | 2 | 2
ICAM1 --+> MMP9 | Expression | Specificity of the blocking effect of anti-LFA-1 and anti-ICAM-1 was demonstrated by the inability of anti-ICAM-2, alone or with anti-LFA-1, to inhibit expression of MMP-9., Anti-ICAM-1 monoclonal antibody prevents the ischemia-induced raise of MMP-9 in brain. (A) Zymography showing [NAME] (95-kDa, 88-kDa, and dimers of high molecular weight)., Because ICAM-1 engagement by ligand or antibody stimulates [NAME] expression (Aoudjit et al., 1998), we reasoned that [NAME] might provide a candidate protease for the proteolytic cleavage and shedding of ICAM-1. <more data available...> | 9510201:1202, 14663338:1202, 12149643:1087, 9725228:1156, 15217903:1203, 11590195:1031 | 2 | 6
ICAM1 --+> vascularization | Regulation | Furthermore, sICAM-1 may enhance tumor growth by promoting angiogenesis and escape from immunosurveillance., However, the regulation mechanisms of [NAME]-induced angiogenesis mediated by ICAM-1 remain unclear., Intercellular adhesion molecule-1 (ICAM-1) is thought to be involved in the processes of metastasis and angiogenesis in various tumors., Intercellular adhesion molecule (ICAM)-1 is increased in various human tumors, and is thought to be involved in the processes of metastasis and angiogenesis. <more data available...> | 10537287:5, 15147829:1, 18339430:2, 14615040:2, 17393097:14, 19306055:0, 9194210:9, 10323764:6, 10823350:7, 20616316:1344 <more data available...> | 2 | 32
ICAM1 ---> arteriogenesis | Regulation | ICAM-1 upregulation may substitute for MCP-1 signaling through [NAME] in order to allow normal arteriogenesis in CCR2 -/- mice., Thus, ICAM-1 is not only important for stimulation of arteriogenesis induced by the infusion of monocyte chemoattractants, but it also appears essential for monocyte adhesion and transmigration during the time course of collateral artery growth., This apparently contradicts ICAM-1-driven arteriogenesis,29 because this selectin mediates leukocyte attachment or transmigration and favors the growth of collateral vessels.22 Nevertheless, other substances, such as leptin,30 have shown the capacity to stimulate arteriogenetic remodeling in the absence of a significant inflammatory macrophage-driven arterial growth. <more data available...> | 15472609:10, 15059933:1175, 20056909:1222, 16684892:1033 | 2 | 4
ICAM1 ---> Breast Neoplasms | Regulation | The interaction between [NAME] and ICAM-1 may be critical to the process of bloodborne metastases in breast cancer., Thus, the study suggests that blocking of OPN-induced ICAM-1 expression through mTOR/p70S6 kinase signaling may be an important therapeutic target for the management of breast cancer. | 8797599:4, 20459645:1364 | 2 | 2
ICAM1 ---> endothelial cell activation | Regulation | Furthermore, studies utilizing knockout mice and specific monoclonal anti-VCAM-1 antibodies have demonstrated that expression of ICAM-1, P-selectin, E-selectin and VCAM-1 are important in in vivo antiphospholipid-mediated thrombosis and endothelial cell activation in mice., ICAM-1 expression in human umbilical vein endothelial cells also was promoted by a 47-kDa integral membrane lipoprotein purified from T. pallidum, implicating a role for spirochete membrane lipoproteins in endothelial cell activation., Thus, we propose that in addition to acting as a leukocyte adhesion molecule, ICAM-1 directly contributes to inflammatory responses within the blood vessel wall by increasing endothelial cell activation and augmenting atherosclerotic plaque formation. | 12892395:10, 1347056:4, 19307690:6 | 2 | 3
ICAM1 ---> endothelial cell proliferation | Regulation | lactosylceramide stimulates the expression of CD11/CD8, or Mac-1, on the surface of human neutrophils and orchestrates a signal transduction pathway that leads to vascular endothelial cell proliferation by a redox-dependent transcriptional pathway that is mediated by the expression of tumor necrosis factor a -induced nuclear factor ?B and intercellular adhesion molecule (ICAM-1) (Chatterjee, 1998). | 12202378:1150 | 2 | 1
IL1A --+> Breast Neoplasms | Regulation | IL-1a therefore, may constitute an effective and rational target to treat pre-invasive and invasive human breast malignancies., Interleukin-1 alpha promotes tumor growth and cachexia in MCF-7 xenograft model of breast cancer., IL1A is thought to contribute to breast cancer expression by up-regulating pro-metastatic genes in breast cancer cells and stromal cells [65]., In IL-1a-stimulated human breast cancer cells (MCF-7), addition of E2 at 10-12 M to 10-9 M (IC50, 5 x 10-11 M) inhibited MCP-1 production in a dose-dependent manner (224). | 16619041:1189, 14633625:100, 16842617:1155, 17640948:1714 | 2 | 4
IL1A --+> ICAM1 | Expression | IL-1 alpha-induced ICAM-1 expression may play an important role in the adhesion process., Levels of ICAM-1 mRNA were also up-regulated by tumour-secreted IL-1alpha., Finally, both lipopolysaccharide and IL-1 alpha up-regulated ICAM-1 and VCAM-1 gene expression., IL-1alpha increased ICAM-1,VCAM-1, and E-selectin expression compared to controls., Stimulation of hepatocytes with IFN-gamma and IL-1 alpha for 24 hr resulted in an increase of ICAM-1 expression., Exposure to IL-1 alpha or TNF alpha resulted in an increased expression of VCAM-1, ICAM-1, and E-selectin. <more data available...> | 14766082:7, 9374368:3, 8004813:7, 12923654:8, 7709438:5, 8649201:3, 8096222:8, 9229375:5, 7521369:7, 10741905:3 <more data available...> | 2 | 56
IL1A --+> ITG | Expression | IL-1alpha upregulated the expression of alpha6 and [NAME] integrins without any alterations of alpha5 and alphav integrins expression., Alteration of integrins by interleukin-1alpha in human pancreatic cancer cells., For instance, interleukin-1a could increase the expression of MMP-9, E-selectin, integrin-1, and IL-8 and inhibit plasminogen activator inhibitor-1 (34, 50-53)., We found that macrophages from FcgammaRIIB-/- mice were hyperresponsive to stimulation with IgG ICs, leading to augmented release of a proinflammatory mediator, IL-1alpha (Fig. 5), that is able to upregulate integrins and vascular adhesion molecules. | 16504015:3, 11668210:100, 14679213:1322, 9874575:1194 | 2 | 4
IL1A --+> ITGB1 | Expression | IL-1alpha upregulated the expression of alpha6 and [NAME] integrins without any alterations of alpha5 and alphav integrins expression., IL-1 alpha and TNF-alpha induced heterogeneous modulation of beta 1 integrin expression in the four melanoma cell lines tested; downward shift of the alpha 2, alpha 3, alpha 4, and beta 1 integrin subunits was detected among three of the melanoma cell lines as were upward shifts of the alpha 4, alpha 5, and alpha 6 integrin subunits among three of the melanoma cell lines., We previously reported that expression of only two subunits, a6- and ß1-integrins, was enhanced by interleukin-1a, and adhesion and invasion to laminin, putative ligand of a6ß1-integrin, was also enhanced by interleukin-a (Sawai et al., 2003a). | 16504015:3, 8006453:6, 16407822:1203 | 2 | 3
IL1A --+> LEP | Expression | In comparison with controls, leptin production was stimulated to 320 +/- 16% (P < 0.0001) and 195 +/- 3.2% (P < 0.0004) by 3 and 10 ng/ml of interleukin-1alpha respectively. 17beta-oestradiol 10(-6) to 10(-9) mol/l increased basal leptin production 5-9-fold, while 10(-5) mol/l had no such effect., IL-1alpha and TNF-alpha treatment significantly stimulated leptin secretion and leptin mRNA expression in explant culture of human term placental tissue and in BeWo cells as compared with those in vehicle controls (P<0.05, for all comparisons). <more data available...> | 10541571:5, 15118268:7, 14633625:9, 11231368:1254, 10068609:1074, 9284748:100, 16131609:1066, 14993491:1189, 10830276:1040 | 2 | 9
IL1A --+> MMP2 | Expression | In addition 12-O-tetradecanoylphorbol-13-acetate and interleukin-1 alpha also increased 72-kDa gelatinase activity., Interleukin-1 alpha produces a dose-dependent several-fold elevation of gelatinase B, stromelysin, and TIMP1 without changing gelatinase A levels., Although Il-1 alpha had no significant effect on TIMP-2 mRNA or on expression of 72-kDa gelatinase, in either early or late passage cells, Il-1 alpha increased the level of a TIMP-2-72-kDa gelatinase complex., Inclusion of Dec-RVKR-CH2Cl with interleukin-1a/OSM resulted in a reduction of the levels of active MMP-2. <more data available...> | 1435512:5, 8225873:6, 8020585:4, 12687549:1298, 11820363:100, 17907161:1127, 9492070:1175, 14581361:1049, 10377072:1173 | 2 | 9
IL1A --+> MMP9 | Expression | MMP3 and MMP9 mRNAs were also inducible in these cells by IL-1alpha stimulation., The IL-1alpha-stimulated MMP9 messenger RNA production was suppressed by cortisol but not P., Pathophysiologic concentrations of interleukin -1alpha rapidly induced pro-MMP-9 synthesis by human skin., Recombinant IL-1alpha upregulated the expression of both [NAME] and -13, and the induction of MMP-13 but not [NAME] could be inhibited by SB203580, an inhibitor of p38., IL-1alpha potently activated NF-kappa B in VSMCs and acted synergistically with growth factors to upregulate expression of MMP-1, -3 and -9. <more data available...> | 11330935:5, 18722610:6, 16291395:5, 14631115:5, 11376631:6, 18274772:6, 10509643:11, 15102045:9, 9046999:5, 8314909:0 <more data available...> | 2 | 17
IL1A --+> vascularization | Regulation | Interleukin -1alpha plays an important role in colon cancer progression and angiogenesis., [NAME] administration of 3 pmol of IL-1 alpha or IL-8 caused intense neovascularization., VEGFR-1 blocking antibodies had a marginal inhibitory effect on IL-1alpha-induced angiogenesis., Moreover, we show that IL-1alpha enhanced colorectal neoplasia, stimulating cell migration and neoangiogenesis., In contrast, blockade of IL-1alpha inhibited both human umbilical vein endothelial cell proliferation and angiogenesis., Interleukin -1a and hepatocyte growth factor (HGF) play an important role in pancreatic cancer proliferation, angiogenesis, and invasiveness. <more data available...> | 19204921:0, 7538184:5, 12205052:9, 17371964:5, 18395750:7, 20872950:0, 7515856:5, 15084984:6, 9245645:1, 21270123:0 <more data available...> | 2 | 31
IL1A --+> VEGFA | Expression | Addition of exogenous Interleukin1 alpha, but not IL6, significantly increased VEGF production., Interleukin-1alpha induced vascular endothelial growth factor production in a dose-dependent and time-dependent manner., Moreover, IL-1 alpha and IL-1 beta enhanced VEGF and iNOS expression by murine peritoneal macrophages., The induction of VEGF expression by prostaglandin E2 and interleukin-1 alpha may be an important mechanism in inflammatory angiogenesis., Levels of VEGF secreted by gastric cancer cells appear to be regulated by IL-1alpha through interleukin-1 receptor Type 1 and were correlated with liver metastatic potential. <more data available...> | 15745939:12, 19210337:8, 19458323:8, 7556649:4, 18395750:5, 9701011:3, 10896254:6, 10629075:8, 10369746:5, 15004178:1294 <more data available...> | 2 | 27
IL1A --+> VEGFC | Expression | Tumor necrosis factor-alpha and IL-1alpha also elevated VEGF-C mRNA steady-state levels, whereas the Interleukin-1 receptor antagonist and dexamethasone inhibited the effect of IL-1beta., It is known that the level of VEGF-C mRNA is upregulated by various factors including IL-1a (Ristimaki et al. 1998). | 9525952:6, 16954441:1244 | 2 | 2
IL1A ---> endothelial cell activation | Regulation | Activation of ECs by complement depended on the autocrine action of IL-1alpha, because complement-mediated endothelial cell activation was inhibited by anti-IL-1alpha antibodies., Accordingly, endothelial cell activation by the membrane attack complex depends on both transcriptional regulation of IL-1alpha and availability of that cytokine to broadly modify endothelial cell physiology., Differential regulation of endothelial cell activation by complement and interleukin 1alpha., For example, it is unclear whether an E-associated increase in C-reactive protein reflects a true increase in the expression of proinflammatory cytokines (IL-1a and IL-6) and subsequent cytokine-mediated endothelial cell activation or whether it is simply due to a direct effect of E on hepatic synthesis of C-reactive protein. | 10769290:5, 18292602:4, 16514066:100, 11549652:1066 | 2 | 4
IL1A ---> endothelial cell proliferation | Regulation | In contrast, blockade of IL-1alpha inhibited both human umbilical vein endothelial cell proliferation and angiogenesis., In contrast, blockade of IL-1alpha or IL-8 inhibited human umbilical vein endothelial cell proliferation and angiogenesis., IL-1a is known to inhibit endothelial cell proliferation, and thereby to promote the type of endothelial injury that is thought to precipitate atherogenesis ([NAME], 1986)., [NAME] expression in endothelial cells is selectively induced by ICs (IFN-gamma, IL-1alpha, IL-1ß and TNF-alpha), which have been shown to inhibit endothelial cell proliferation and induce adhesion of leukocytes to these cells. | 18395750:7, 15084984:6, 12615956:1306, 12881412:1042 | 2 | 4
IL1B --+> Breast Neoplasms | Regulation | Interleukin-1beta and fibroblast growth factor receptor 1 cooperate to induce cyclooxygenase-2 during early mammary tumourigenesis. | 19393083:100 | 2 | 1
IL1B --+> endothelial cell activation | Regulation | Anti-CD14 antibodies did not affect endothelial cell activation induced by IL-1 beta, tumour necrosis factor-alpha (TNF-alpha) and phorbol 12-myristate 13-acetate (PMA)., This inhibitory effect of N,N,N-trimethylsphingosine on IL-1 beta-dependent endothelial cell activation may partly explain the known anti-inflammatory or anti-metastatic effect of N,N,N-trimethylsphingosine in vivo., We conclude that TNF-alpha and IL-1 beta induced in whole blood by picomolar concentrations of LPS mediate endothelial cell activation to these small quantities of LPS and that blocking of both cytokines is necessary to inhibit LPS-induced blood-dependent endothelial cell activation. <more data available...> | 7503948:6, 7540991:4, 7583352:7, 9607219:1148, 14581484:1366, 10528660:1251, 19213954:1231 | 2 | 7
IL1B --+> endothelial cell proliferation | Regulation | In addition, PEDF inhibits the VEGF-and IL-1beta-induced endothelial cell proliferation, migration and tube formation. | 20006737:7 | 2 | 1
IL1B --+> ICAM1 | Expression | TNF-alpha and IL-1 beta also increased the expression of ICAM-1 on MMG2., IFN-gamma, IL-1 beta and TNF-alpha produced a clear enhancement of ICAM-1 expression., Interleukin -1beta mainly up-regulated ICAM-1 expression., Sulprostone, an EP1/EP3 agonist, had no effect on IL-1beta-elicited ICAM-1 expression., The treatment with IFNgamma or IL-1beta enhanced the expression of CD54., IL-1beta increased the expression of ICAM-1 at the mRNA and protein levels in ARPE-19 cells., Antibody to interleukin-1beta reduced baseline and rhinovirus-induced ICAM-1 production. <more data available...> | 8097520:4, 1373059:3, 16734619:3, 11201045:9, 15499832:3, 16822504:5, 15733557:3, 15389584:5, 17275031:8, 17029006:4 <more data available...> | 2 | 104
IL1B --+> ITG | Expression | These findings suggest that human IL-1 beta differentially regulates expression of integrins., Under substrate adherent conditions, [NAME] expression can be regulated by transforming growth factor-beta, interleukin-1 beta, and prostaglandins., Thus, IL-1 beta and TGF-beta 1, which usually have antagonistic functions in connective tissue, can regulate integrin expression in a synergistic way., Recombinant human IL-1 beta inhibits human osteosarcoma cell proliferation, stimulates [NAME], and induces alkaline phosphatase activity, a marker of osteoinductive and osteoblastic phenotype. <more data available...> | 1748714:3, 1429694:0, 1744142:10, 2786815:1, 17702847:1255, 10458713:1158, 7543825:1172 | 2 | 7
IL1B --+> ITGB1 | Expression | GFs or BMS-345541 (specific inhibitor of the IKK) reversed the IL-1ß-induced down-regulation of collagen type II, cartilage specific proteoglycans, [NAME], Shc, activated MAPKinase, Sox-9 and up-regulation of active caspase-3., Production of IL1-beta by ovarian cancer cells induces mesothelial cell [NAME]-integrin expression facilitating peritoneal dissemination., Monomeric collagen and PDGF-BB/interleukin-1ß co-stimulation induced p66Shc expression and Ser36-phosphorylation through ß(1) [NAME] and PDGF receptor-ß, respectively. | 22194879:6, 22296757:100, 22770800:7 | 2 | 3
IL1B --+> MMP2 | Expression | MMP-2 mRNA expression was significantly upregulated by IL-1beta (4 ng/ml and 10 ng/ml, all P<0.01)., SN50, NF-kappaB inhibitor peptide, inhibited IL-1beta-stimulated increases in MMP-2 and -9 expression and activity., TNF-alpha, IL-1beta, and IL-6 increased the mRNA and/or protein expression of MMP-1, MMP-2, and MMP-3., Overexpression of IL-1beta resulted in augmentation of expression of the cytokines, ICAM-1, and matrix metalloproteinase-2 (MMP-2)., Interleukin-1 beta up-regulated the levels of MMP-1 and MMP-2, but it did not alter the expression of extracellular Matrix metalloproteinase inducer. <more data available...> | 19671357:6, 15269222:11, 16934628:5, 12824917:3, 19602123:9, 12592549:10, 16987994:7, 14638701:9, 15272234:6, 8756539:5 <more data available...> | 2 | 39
IL1B --+> MMP9 | Expression | IL-1ß has been reported to induce matrix metalloproteinase-9 (MMP-9) expression., Moreover, TNF-alpha as well as IL-1 beta induced the expression of MMP9., [NAME] messenger RNA was dramatically decreased by IL-1beta only in low oxygen tension., Both IL-1beta and TNF-alpha augmented [NAME] expression in HT1080 cells., IL-1beta enhanced nuclear factor [NAME], [NAME] expression, and the invasive ability of GCTM-1., Similarly, quantitative RT-PCR found that TNF and IL1B enhanced [NAME], but not MMP2, mRNA levels. <more data available...> | 21199898:5, 9631748:7, 15529381:11, 11747375:7, 15014040:5, 18276934:9, 11067938:7, 11825017:11, 15269222:11, 19097983:3 <more data available...> | 2 | 109
IL1B --+> NOTCH2 | Regulation | Induction of nestin, LIF and Notch-2 by interleukin-1ß/transforming growth factor-ß can be reverted after cytokine withdrawal. | 22330721:6 | 2 | 1
IL1B --+> vascularization | Regulation | We examined the association between IL-1beta-induced angiogenesis and cell inflammation., However, dexamethasone's impact on interleukin -1beta-dependent inflammatory angiogenesis is unknown., This is the first report that [NAME] and some prostanoids play a key role in IL-1beta-induced angiogenesis., IL-1 beta-induced angiogenesis was markedly reduced in monocyte chemoattractant protein-1 knockout mice., It is understood that interleukin -1beta increases remarkably in ischemic tissue and has particular effects on angiogenesis. <more data available...> | 16239969:2, 17690185:1, 14769824:7, 16227824:9, 16936436:1, 15202019:7, 12057931:10, 21435467:9, 16129959:4, 15126358:13 <more data available...> | 2 | 73
IL1B --+> VEGFA | Expression | IL-1beta increased the activity of the VEGF promoter-reporter construct., IL-1beta regulated VEGF-A and angiopoietin-1 expressions in a dose-dependent manner., In contrast, TBF-beta and IL-1beta caused an increase in VEGF production., Furthermore, IL-1beta synergistically enhanced the effect of OSM on VEGF production., Treating TMK-1 cells with IL-1beta also increased VEGF promoter activity., triamcinolone acetonide suppressed VEGF expression induced by IL-1b in Müller cells at the transcriptional level., IL-1beta induced transcripts of IL-1beta, IL-6, IL-8, VEGF, MMP3, and MCP-1. <more data available...> | 10408390:9, 16565972:12, 11423727:9, 17525365:9, 15349119:8, 16049703:12, 18758357:10, 12789234:8, 15126358:8, 11040101:5 <more data available...> | 2 | 107
IL1B --+> VEGFC | Expression | IL-1beta and tumor necrosis factor-alpha also stimulated the production of VEGF-C protein by the fibroblasts., We found that proinflammatory cytokine, interleukin-1beta (IL-1beta), could induce lymphangiogenesis in mouse cornea through enhanced production of potent lymphangiogenic factors, VEGF-A, VEGF-C and VEGF-D., Our results suggest that [NAME] acid-stimulated lymphangiogenesis in human umbilical vein endothelial cells is mediated through Interleukin-1ß-induced VEGF-C expression., Furthermore, IL-1beta-induced p38 mitogen-activated protein kinase activation and upregulation of VEGF-C mRNA and protein in [NAME] lung carcinoma cells was also suppressed by artemisinin or by the p38 mitogen-activated protein kinase inhibitor SB-203580, suggesting that p38 mitogen-activated protein kinase could serve as a mediator of proinflammatory cytokine-induced VEGF-C expression. <more data available...> | 9525952:9, 18951870:1, 21151531:6, 18667841:4, 12471041:1198, 14603252:1077, 19237567:1054, 12915657:1183, 17015745:1177, 16570043:1238 | 2 | 10
IL1B ---> blood vessel development | Regulation | IL-1ß disrupted pulmonary vascular development and decreased the production of VEGF. | 16888287:1238 | 2 | 1
IL1B ---> Breast Neoplasms | Regulation | Interleukin-1ß (IL-1ß), which is involved in inflammatory and immunological responses, plays an important role in the development and progression of breast cancer., The inflammatory chemokines CCL2 (MCP-1) & CCL5 (RANTES) and the inflammatory cytokines TNFa & IL-1ß were shown to contribute to breast cancer development and metastasis., These studies demonstrate that tumor-associated IL-1alpha+, IL-1beta are present in the tumor microenvironment and may play a pivotal role in regulating breast tumor growth and metastasis. <more data available...> | 20437198:0, 21486440:0, 9864403:4, 12127053:1, 19393083:100, 18708360:1055, 16148018:1190 | 2 | 7
IL1B ---> endothelial cell proliferation | Regulation | In addition, PEDF inhibits the VEGF-and IL-1beta-induced endothelial cell proliferation, migration and tube formation., Sera were then assayed for immunologically detectable IL-1ß by ELISA. (C) Systemic neutralization of IL-1ß significantly inhibits Myc-induced islet endothelial cell proliferation., When compared to the positive control value derived from the cells stimulated with [NAME], both interleukin-1ß and conditioned media showed a strong stimulatory influence on corneal endothelial cell proliferation. <more data available...> | 20006737:7, 16980582:1200, 19136710:1266, 12881412:1042 | 2 | 4
IL1B ---> endothelialization | Regulation | Furthermore, it is unlikely that reendothelialization after vascular injury is influenced by the ASC-regulated inflammatory cytokines interleukin-1ß and IL-18. | 18541743:1241 | 2 | 1
IL1B ---> ITGB1 | Expression | The suppression of collagen type II and beta1-integrin synthesis by IL-1beta was inhibited by curcumin., Incubation of chondrocytes with IL-1ß resulted in induction of apoptosis, downregulation of ß1-integrins and the extracellular signal-regulated kinase 1/2 ., Resveratrol significantly reduced the IL-1beta-induced inhibition of expression of cartilage-specific collagen type II and signal transduction receptor [NAME]-integrin in a time-dependent manner., [NAME] beta and TNF alpha down regulated the expression of the alpha 6 and beta 1 integrin subunits on long term cultures of fibroblast-like synoviocytes derived from rheumatoid arthritis. <more data available...> | 16320828:8, 21484156:5, 17404069:5, 9849316:9, 2521862:6 | 2 | 5
IL1B ---> NOTCH1 | Regulation | Additionally, the Notch1 upregulation mediated by IL-1ß could facilitate NF-?B activation, thus downregulating I?Ba expression., The ?-secretase-mediated S3 cleavage of Notch is enhanced by TNF-a, IL-1ß, and IFN-?. | 17881497:1221, 15347683:1147 | 2 | 2
IL1B ---| NOTCH3 | Expression | Indeed, this cytokine modulates Notch signaling components and expression of inflammatory enzymes simultaneously ([NAME], 1999[Go]; [NAME], 2004[Go]), and a mutated form of I?Ba blocking dissociation of the NF-?B complex prevents the IL-1ß-induced inhibition of Notch3 and [NAME] and enhancer of split1 gene expression ([NAME]. 5B). | 17881497:1205 | 2 | 1
ITG --+> Breast Neoplasms | Regulation | Targeting a(V)-integrins decreased metastasis and increased survival in a nude rat breast cancer brain metastasis model. | 22842979:100 | 2 | 1
ITG --+> IL1A | Expression | We conclude that [NAME] leads to Erk activation and increased IL-1alpha expression by potentiating activation of the EGF receptor., We have previously shown that [NAME] results in activation of Erk MAPK and increased IL-1a production (Haase et al, 2001; Hobbs and Watt, 2003)., Regulation of interleukin-1a expression by integrins and epidermal growth factor receptor in keratinocytes from a mouse model of inflammatory skin disease., Hobbs, RM, [NAME], FM: Regulation of interleukin-1a expression by integrins and epidermal growth factor receptor in keratinocytes from a mouse model of inflammatory skin disease. | 12654926:7, 15304090:1145, 18766172:1422, 16354192:1373 | 2 | 4
ITG --+> IL1B | Expression | The results indicate that monocyte adhesion was affected by the substrate and the RGD sequence and [NAME] or beta3 containing integrin receptors. beta1- or beta3-containing integrin receptors were also involved in IL-1beta gene and protein expression in monocytes adhered to gelatin-based biomaterial surfaces., Regulation of IL-1ß mRNA by integrins in bovine chondrocytes., Inhibition of adhesion- and integrin ligation-induced tyrosine phosphorylation and interleukin-1ß mRNA expression by herbimycin A or genistein. <more data available...> | 17623553:11, 10679109:1210, 7541794:1226, 20543863:100, 9062344:1075, 11489912:1122, 12121221:1031 | 2 | 7
ITG --+> MMP2 | Expression | We also examined which integrins mediated the expression and secretion of matrixins MMP-2 and [NAME]., [NAME] of the signal activity of the integrins by RGD-containing pentapeptide or by genistein reduces markedly in vitro invasion in Matrigel and MMP-2 production., Expression of MMP-2, [NAME]matrix metalloproteinase and TIMP-2 was affected by IR and anti-integrin treatment., These data indicate that OPN, uPA and MMP-2 promoter activities are regulated by [NAME] of OPN as an RGD-containing ligand, ILK activation and AP-1 DNA binding/transactivation. <more data available...> | 12177247:7, 15236606:5, 14647148:1227, 16474180:1292, 10429943:100, 17018612:1072 | 2 | 6
ITG --+> MMP9 | Expression | We also examined which integrins mediated the expression and secretion of matrixins MMP-2 and [NAME]., In addition, engagement of integrin receptors by the disintegrin-cysteine-rich domain resulted in ERK phosphorylation and increased [NAME] synthesis., Expression of MMP-9 was elevated by [NAME], [NAME] ectodomain shedding was inhibited by a MMP-9 function blocking antibody, and incubation of cells with exogenous [NAME] catalyzed E-cadherin ectodomain shedding., Similarly, addition of integrins inhibitor to human umbilical vein endothelial cells suppressed the stress-induced [NAME] expression, IkappaBalpha degradation, NF-kappaB DNA-binding activity and the phosphorylation of p38 mitogen-activating protein kinase, extracellular signal-regulated kinase1/2. <more data available...> | 12177247:7, 17704059:6, 17332331:5, 17174275:5, 15728252:1251, 12874388:1215, 16636068:1353, 19272161:1188, 11073115:1238, 20103658:1302 <more data available...> | 2 | 15
ITG --+> vascularization | Regulation | [NAME] v integrins are thought to play an important role in tumor angiogenesis., [NAME] and alphavbeta5 are involved in angiogenesis., It is not known which integrins are involved in the initial stages of angiogenesis in vivo., Furthermore, our data provide a novel method by which an integrin may regulate angiogenesis., It is becoming clear that integrins regulate angiogenesis in both a positive and negative manner., Integrin signaling also plays a key role in tumor growth, angiogenesis, and metastasis. <more data available...> | 16835373:0, 17497369:1, 8077704:1, 20639457:5, 16307488:2, 18221059:2, 14760364:2, 15911748:0, 9787163:0, 15777239:6 <more data available...> | 2 | 112
ITG --+> VEGFA | Expression | These findings reveal that integrin-mediated activation of PI-3K-Akt is amplified by integrin-stimulated VEGF expression and they provide a mechanism that substantiates the reported role of alpha 6 beta 4 in carcinoma progression., This finding prompted us to evaluate the mechanism by which this integrin contributes to VEGF transcription., In addition, integrin-matrix interactions modulate expression of VEGF and fibroblast growth factor receptor 1 and 2 expression on HMVEC (36)., In a breast carcinoma cell line, integrin-mediated signalling increased VEGF mRNA loading on polysomes ([NAME], 2002). <more data available...> | 12105188:5, 15256436:1146, 15590642:1286, 15580293:1048, 17483349:1406, 16565398:100, 16921028:1068, 17426256:1250, 23150625:6 | 2 | 9
ITG ---- VEGFC | Binding | Importantly, this complex seems to be operative in vivo because an antibody anti-a9ß1 integrin partially reduces the angiogenic effect of VEGF-A.42 The same integrin has been reported to interact with VEGF-C, VEGF-D, and HGF, a finding that may help explain the abnormal lymphatic phenotype of mice expressing a null mutation of the a9 subunit.43,44 Similar observations have been reported for a3ß1 and avß3;45 these integrins bind to VEFG-A165 and VEGF-A189, but not to the shorter isoform VEGF-A121 allowing EC migration and survival in a VEGF receptor-independent way (Figure 3). | 18285512:1100 | 2 | 1
ITG ---- VEGFR ligand | Binding | Integrins bind angiogenic modulators. 3.1 Integrins bind vascular endothelial growth factors. | 18285512:1095 | 2 | 1
ITG ---> blood vessel development | Regulation | These integrins on other cells, and/or other integrins on endothelial cells, might contribute to fibronectin assembly and vascular development., Vascular development and maturation are dependent on the interactions of endothelial cell integrins with surrounding extracellular matrix., Various integrins are expressed on trophoblast membrane and participate in placenta anchoring, cell adhesion , migration and vascular development., Our results demonstrate for the first time that the alpha7beta1 integrin is important for the recruitment or survival of cerebral vascular smooth muscle cells and that this integrin plays an important role in vascular development and integrity. <more data available...> | 20570943:9, 12067900:0, 20018348:0, 16003770:9, 15576410:6, 12454288:6, 12370271:1060, 12370267:1054, 18351655:1525 | 2 | 9
ITG ---> Breast Neoplasms | Regulation | The alphaV integrins play major roles in favouring breast cancer spreading., The integrin family of cell adhesion receptors is essential to breast cancer progression., This PRLr-SIRPa-integrin complex may therefore provide a basis for integrin-PRLr cross-talk and contribute to the biology of breast cancer., In this review, we highlight recent advances in our understanding of how integrins regulate breast cancer through modulation of the actin cytoskeleton and the mechanisms that regulate this process., It has been proposed that cross talk between integrin and growth factor receptor signaling such as ErbB2 (HER2) is required for activation of downstream effectors and ErbB2-mediated mammary tumorigenesis. <more data available...> | 10708943:1, 18363848:2, 20826546:9, 20112053:4, 19147560:0, 12908817:11, 8576205:7, 16904607:100, 11172040:100, 14759991:1051 <more data available...> | 2 | 24
ITG ---> endothelial cell proliferation | Regulation | In retinal angiogenesis, hypoxia is the initial stimulus that causes up regulation of growth factors, integrins and proteinases, which result in endothelial cell proliferation and migration that are critical steps in this process., The extracellular binding of NK4 to perlecan inhibits cell-associated assembly of fibronectin, and the impaired fibronectin assembly suppresses integrin-dependent angiogenic responses, i.e., endothelial cell proliferation, migration and tube formation., [NAME], a platelet glycoprotein Ib binding protein from [NAME] acutus venom, could sustain human umbilical vein endothelial cell proliferation and human umbilical vein endothelial cell adhering to immobilized agglucetin showed extensive spreading, which was strongly abrogated by integrin antagonists 7E3 and [NAME]. <more data available...> | 14575722:2, 20015005:4, 18312855:0, 12063036:10, 17616733:1229, 16186806:1165, 14555703:1263, 21474814:0 | 2 | 8
ITG ---> endothelialization | Regulation | RGD peptides completely prevented VEGF-induced cell migration (data not shown), indicating that VEGF-stimulated reendothelialization also depends on integrins., Thus, inhibition of avß3- and avß5-integrins with cyclic RGD peptides blocked reendothelialization of denuded arteries in vivo, suggesting that avß3- and avß5-integrins are involved in the reendothelialization of injured carotid arteries.51 However, other integrins such as the ß1-integrins may also mediate adhesion of progenitor cells to extracellular matrix proteins during reendothelialization of denuded arteries.13 . | 11788463:1091, 15321944:1154 | 2 | 2
ITG ---> vasculogenesis | Regulation | Moreover, the [NAME] hybridization signal was detected in developing cartilages but not in ossified or ossifying bones. beta5-Integrin is a key integrin involved in angiogenesis, vasculogenesis, hematopoiesis, and bone formation., beta8 integrins are required for vascular morphogenesis in mouse embryos., In vivo, integrins have been shown to be involved in both angiogenesis and vasculogenesis., Thus, we speculate that avß3-integrins might have an important role in vasculogenesis as an initial trigger in our model. <more data available...> | 11936189:9, 12050137:100, 9022067:1067, 16754788:1134, 16251442:1071, 17363377:1241, 18184864:1271, 16306453:1163, 15618543:1046 | 2 | 9
ITGB1 --+> blood vessel development | Regulation | We show that endothelial ß1 integrin plays a crucial role in vascular development and patterning., Although it is notable that ß1-null mice fail to develop a vasculature (51), it is unclear which ß1 integrin plays the most critical roles in vascular development., We provide direct evidence of a link between Notch and ß1 integrins involving R-Ras activation that may represent a central mechanism for regulation of vascular development and angiogenesis., Indeed, function-blocking ß1-integrin antibody CSAT has been reported to disrupt vascular development and lumen formation when microinjected into quail embryos (18), whereas the same CSAT antibody does not affect FGF-2- or tumor necrosis factor alpha-induced angiogenesis in the chick chorioallantoic membrane (10). | 17984225:1061, 12364323:1304, 17664272:1284, 11909975:1428 | 2 | 4
ITGB1 --+> Breast Neoplasms | Regulation | These findings show that beta1 integrin expression has potential prognostic value in invasive breast cancer and that coexpression of fibronectin may help identify patients with more aggressive tumors who may benefit from targeted therapy., [NAME] inhibition dramatically enhances radiotherapy efficacy in human breast cancer xenografts., Indeed, expression of ß1 integrin was shown recently to be necessary for formation of mammary tumors in engineered murine models (4)., In addition, inhibition of ß1 integrin function decreases the number and size of metastases in a mouse mammary carcinoma model (56) and decreases the malignancy of several breast cancer cell lines (57). <more data available...> | 17234776:6, 18519702:100, 16452209:1272, 19435818:1347, 16357126:1141, 19147559:1299, 18056629:1035, 18268536:1171, 19147981:1066 | 2 | 9
ITGB1 --+> MMP9 | Expression | In addition, the hypoxia induced increase of F-actin distribution and cell migration (activation of matrix metalloproteinase-2 and -9) was inhibited by [NAME] antibody., Bombesin-dependent [NAME] activation in prostatic cancer cells requires [NAME] integrin engagement., Stack showed that in oral squamous cell carcinoma, multivalent aggregation of a3ß1 integrins up-regulates both [NAME] and [NAME] expression., [NAME] of tumor growth due to matrix metalloproteinase-9 inhibition is mediated by sequential activation of [NAME]-integrin, ERK, and NF-kappaB. <more data available...> | 20677223:6, 12372334:100, 12907660:1137, 17991734:100, 18940913:1146, 11073115:1217, 11557738:1198, 16798740:1280 | 2 | 8
ITGB1 --+> vascularization | Regulation | These effects were correlated with the reduced expression of [NAME] (ITGB1), an important signaling component of angiogenesis., The alpha(v)beta(3)- and [NAME] play a key role in angiogenesis, the formation of new vessels in tissues that lack them., [NAME] expression blocked local angiogenesis and reduced recovery from neurological deficit., Among the blood vessel markers were endoglin, tie-2, PDGFB, and [NAME], that are important regulators of blood vessel formation. <more data available...> | 21501586:4, 19489579:0, 17651977:8, 11891179:6, 18058911:8, 9914168:5, 11741838:11, 19837065:4, 17161391:8, 19228122:4 <more data available...> | 2 | 37
ITGB1 ---- MMP9 | Binding | Our data also suggest that [NAME] and ß1-integrin interact through the carboxyl-terminal hemopexin domain of MMP-9., In our study, only [NAME] could be coprecipitated with [NAME], and CD44 and DMP-1 could not, corresponding with the results of glycolipid-enriched microdomain/rafts fractionation experiments., Since [NAME] may bind to ß1 integrin [39], a competition between [NAME] and collagen for this integrin may occur, leading to reduced collagen gel contraction. | 18048360:1373, 16636068:1366, 15820209:1239 | 2 | 3
ITGB1 ---> endothelial cell proliferation | Regulation | Krit1 modulates beta 1-integrin-mediated endothelial cell proliferation., Induction of endothelial cell proliferation by recombinant and microparticle-tissue factor involves beta1-integrin and extracellular signal regulated kinase activation., Moreover, further issues emerge from molecular studies showing that KRIT1 can regulate either VE-cadherin-mediated endothelial cell-cell junction integrity [15], [16] or ß1 integrin-mediated endothelial cell proliferation [17]. | 18812969:100, 20616308:100, 20668652:1115 | 2 | 3
ITGB1 ---> IL1B | Expression | The ligation of beta 1 integrins with antibodies or F2 fragments also induces the expression of immediate-early genes such as IL-1 beta., The beta(1)-integrin-mediated expression of IL-1beta and IL-6 could contribute to local and systemic inflammatory reactions in atherosclerosis., In MDA-MB231 cells, up-regulation of L1CAM augmented expression of IL-1ß and nuclear factor kappa B activation, which was reversed by depletion of L1CAM, L1CAM-binding membrane cytoskeleton linker protein ezrin, ß1-integrin or focal adhesion kinase (FAK). | 8089188:7, 10669630:9, 22764136:3 | 2 | 3
ITGB1 ---> vasculogenesis | Regulation | Antibodies to ß1-integrins cause alterations of aortic vasculogenesis in vivo., Antibodies to beta 1-integrins cause alterations of aortic vasculogenesis, in vivo. | 16894628:1445, 1540708:100, 11146503:1694 | 2 | 3
ITGB1 ---| VEGFC | Expression | They showed that the loss of NCAM results in the loss of ß1 integrin function, which contributes to loss of tissue integrity, upregulated expression of lymphangiogenic vascular endothelial growth factor-C (VEGFC) and VEGFD, and subsequently increases lymphangiogenesis and the lymphogenic dissemination of tumour cells (Crnic et al, 2004). | 15864290:1053 | 2 | 1
LEP --+> Breast Neoplasms | Regulation | These results suggest that leptin may have an independent role in breast tumorigenesis., [NAME] is a product of the obese gene and plays an important role in breast cancer development., There is evidence that adipokines such as leptin and adiponectin may influence breast tumor development., A recent hypothesis suggests that the adipokines, adiponectin and leptin, are involved in breast cancer development., Breast cancer cell lines, ZR75-1 and HTB-26, were treated with 0, 4, 40 or 80 ng/ml of leptin., This study provides additional evidence that leptin and its cognate receptor may be involved in mammary tumorigenesis. <more data available...> | 19223908:7, 21472316:2, 19723917:0, 19661131:1, 16525650:5, 14734797:12, 15240518:8, 18715880:2, 17409452:0, 16533767:0 <more data available...> | 2 | 38
LEP --+> endothelial cell activation | Regulation | Leptin induces endothelial cell activation, migration, and proliferation [6] and thus applies a proliferative activity on monocytes [7]., Direct leptin-stimulated endothelial cell activation and angiogenesis were previously reported in nonglomerular endothelial cells, but induction of endothelial cell TGF-ß1 synthesis is a novel and important finding., Since the leptin receptor is known to be expressed in ECs derived from human adipose tissue (18) and leptin induces an oxida-tive stress in ECs (30,31), the results of the present study strongly suggest that leptin could elicit endothelial cell activation and the infiltration of circulating blood monocytes into adipose tissue. | 20458445:1045, 10469386:1040, 15111498:1225 | 2 | 3
LEP --+> endothelial cell proliferation | Regulation | There is also evidence that [NAME] stimulates endothelial cell proliferation and the formation of capillary-like tubes in vitro., Pharmacological inhibitors of COX-2, the phosphatidylinositol 3-kinase /Akt pathway and p38(MAPK) abrogated leptin-induced endothelial cell proliferation (assessed by quantifying 5-bromo-2'-deoxyuridine incorporation, calcein fluorescence and propidium iodide staining), slowed the increased migration rate of leptin-stimulated cells (in vitro wound healing assay) and inhibited leptin-induced capillary-like tube formation by human umbilical vein ECs on Matrigel. <more data available...> | 18448353:1, 21533119:5, 11344271:1095, 18779779:1171, 12149466:1161, 10469386:1019, 21877194:3 | 2 | 7
LEP --+> IL1B | Expression | [NAME] increased the expression of IL-1beta mRNA evaluated by RT-PCR., [NAME] injection of leptin induced IL-1beta expression in the hypothalamus., At a functional level, leptin up-regulates the IL-1beta, IL-6, IL-12, TNF-alpha, and MIP-1alpha production., IL-1beta transcripts in the hypothalamus were significantly increased on RT-PCR assessment 1 h after the administration of [NAME] (1 mg/kg iv) to mice., Also, [NAME] had a detrimental effect on chondrocyte proliferation and induced IL-1beta production and [NAME] and MMP-13 protein expression. <more data available...> | 10873603:3, 12676369:3, 15905523:7, 11792675:4, 17350295:7, 17419800:6, 15304373:5, 18547319:8, 20560877:5, 17551224:5 <more data available...> | 2 | 29
LEP --+> ITG | Expression | Leptin-mediated migration and increased integrin expression were attenuated by OBRl receptor antisense oligonucleotide (ODN)., [NAME]-mediated migration and integrin upregulation were attenuated by OBRl receptor antisense oligonucleotide., Future studies will have to examine in more detail how interaction of leptin with its receptor on endothelial (progenitor) cells upregulates specific integrins. | 20945385:4, 19168585:4, 18658052:1201 | 2 | 3
LEP --+> MMP2 | Expression | Accordingly, upon quantitative PCR analysis we found that leptin increased expression of matrix metalloproteinase-2 (MMP-2)., [NAME] significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage., [NAME] (10-40 ng/ml) induced proliferation of the human umbilical vein endothelial cells and elevation of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression in a dose-dependent manner., In summary, our results indicate that leptin induces MMP-2 expression and activity without altering collagen synthesis, suggesting that normal leptin function has the potential to prevent extracellular matrix accumulation. <more data available...> | 16376323:4, 19876764:7, 11460888:7, 16238189:9, 15983226:4, 21220407:3, 11799135:1265, 20133323:1307, 20683677:100, 15306556:1073 <more data available...> | 2 | 13
LEP --+> MMP9 | Expression | Also, [NAME] had a detrimental effect on chondrocyte proliferation and induced IL-1beta production and [NAME] and MMP-13 protein expression., [NAME] also induced increases of MMP-2, MMP-9, TIMP-1, and Up-regulated the human coronary artery smooth muscle cells ., [NAME] significantly increased both gene and protein levels of MMP-2, MMP-9, cathepsin D, and collagen II, while decreased bFGF markedly in cartilage., Using cultures of ovarian explants, [NAME] increased the activity but not the protein expression of MMP-2 and [NAME] in both culture medium and ovarian tissue, and the protein expression of TIMPs, without a higher inhibitory action of the gelatinase activity. <more data available...> | 17350295:7, 11460888:8, 19876764:7, 21220407:3, 11799135:1220, 19620723:1171, 15306556:1073, 11006325:1261, 20723213:1200, 21744298:4 <more data available...> | 2 | 12
LEP --+> NOTCH1 | Expression | In addition, blockade of IL-1R tI inhibited leptin-induced Notch, Hey2 and survivin as well as VEGF/VEGFR-2 expression., [NAME] treatment leads to survivin upregulation, due in part to the activation of Notch1 and the release of a transcriptionally active Notch1 intracellular domain . | 21731759:7, 21555376:6 | 2 | 2
LEP --+> vascularization | Regulation | However, the molecular mechanism for leptin-elicited angiogenesis remains to be elucidated., [NAME] induced angiogenesis in cornea from Zucker lean rats, but not from Zucker fatty rats., [NAME] has been shown to be involved not only in thermogenesis but angiogenesis as well., Leptin induces angiogenesis and is elevated in obesity and hyperinsulinemia., Recently, [NAME] was shown to possess an angiogenic action in vitro and to induce neovascularization in vivo., We conclude that leptin stimulates leukemic cell growth in vivo by promoting angiogenesis. <more data available...> | 12711260:2, 12921973:9, 14724368:3, 12411472:1, 10868868:1, 12393625:11, 20137154:4, 18573568:1, 11494053:2, 11925116:1 <more data available...> | 2 | 112
LEP --+> VEGFA | Expression | Incubation of 4T1 cells with anti-VEGF-R2 antibody increased leptin-mediated VEGF expression suggesting an autocrine/paracrine loop., [NAME] upregulated the transcriptional expression of VEGF/VEGFR2 in MCF-7 and MDA-MB231 cells., The present study suggests that [NAME] could elicit angiogenesis through autocrine VEGF production via intracellular reactive oxygen species generation., Although it did not affect cell growth, leptin significantly up-regulated pericyte messenger ribonucleic acid levels of an endogenous angiogenic stimulator, vascular endothelial growth factor (VEGF). <more data available...> | 16825198:3, 19531256:6, 12711260:9, 12779248:4, 15546570:5, 18821585:4, 15331557:7, 21475828:4, 11152449:1134, 17786229:1142 <more data available...> | 2 | 23
LEP ---> blood vessel development | Regulation | Recent studies have provided evidence that [NAME] has significant effects on vascular development and repair., This is the first study demonstrating that leptin can induce preneoplastic colon epithelial cells to orchestrate VEGF-driven angiogenesis and vascular development, thus providing a specific mechanism and potential target for obesity-associated cancer., Perspective References Although the role of the adipokine leptin in human obesity and insulin resistance has yet to be fully clarified (57), recent studies have provided evidence that [NAME] also has significant effects on vascular development and repair. <more data available...> | 16940932:0, 19221001:10, 15181024:1211, 18292198:1072 | 2 | 4
LEP ---> ICAM1 | Expression | [NAME] could up-regulate cell surface expression of adhesion molecule ICAM-1 and CD18 but suppress ICAM-3 and L-selectin on eosinophils., Leptin blockade also affected expression of ICAM-1, OX-40, and very late antigen-4 on CD4+ T cells (Figure 8)., Lastly, as leptin promotes angiogenesis and induces the expression of bcl-2, intercellular adhesion molecule 1 and matrix metalloproteinases, it could be one of the permissive factors that lead to the development of endometriosis in susceptible patients ([NAME], 2004[Go]). <more data available...> | 17634954:5, 16410832:1141, 16269446:1085, 21040518:1260 | 2 | 4
LEP ---> NOTCH1 | Expression | Moreover, Notch expression is regulated by hypoxia and inflammatory cytokines (IL-1, IL-6 and leptin)., In addition, blockade of IL-1R tI inhibited leptin-induced Notch, Hey2 and survivin as well as VEGF/VEGFR-2 expression., [NAME] treatment leads to survivin upregulation, due in part to the activation of Notch1 and the release of a transcriptionally active Notch1 intracellular domain . | 21193018:2, 21731759:7, 21555376:6 | 2 | 3
LEP ---> vasculogenesis | Regulation | These findings are relevant to leptin-mediated regulation of vasculogenesis in humans, and the association between hyperleptinemia and obesity with cardiovascular disease., In response to hypoxia, adipose tissues produce hypoxia inducible factor 1a-induced angiogenic factors such as VEGF, leptin, TNF-a, and PAI-1, which regulate angiogenesis and vasculogenesis (49, 50). | 15950978:11, 17786229:1102 | 2 | 2
MMP2 --+> vascularization | Regulation | Two members of the family, gelatinase A and B play an important role in angiogenesis., We also demonstrated that MMP-2 is a primary mediator of Amadori-PE-driven angiogenesis., This augmentation of angiogenesis was hindered by inhibition of pro-MMP-2 and mature MMP-2., [NAME], a member of the matrix metalloproteinase family, plays an important role during angiogenesis., Expression of MMP-2 plays an important role in angiogenesis and lymph node metastasis of esophageal cancer., In dermatofibrosarcoma protuberans, MMP-2 may play a role in tumor angiogenesis. <more data available...> | 11470230:3, 14644453:5, 20486790:9, 10785359:0, 15946548:6, 15387709:8, 12566302:0, 10996658:0, 17344928:0, 20492444:2 <more data available...> | 2 | 111
MMP2 ---> arteriogenesis | Regulation | Collectively, these findings suggest that matrix metalloproteinase-2-mediated impairment of arteriogenesis and angiogenesis may be at least partially reduction of VEGF production resulting from the decreased macrophage infiltration in the ischemic hindlimb of MMP-2-/- mice., Matrix metalloproteinases have been shown to mediate nitric oxide-induced cadherin/ß-catenin dissociation.29,30 In addition, at least 2 members of the Matrix metalloproteinases family, Matrix metalloproteinase-2 (72 kDa) and Matrix metalloproteinase-9 (92 kDa), play an essential role in vasculogenesis, angiogenesis, and arteriogenesis, 3 processes critical to restoration of tissue perfusion after ischemia.31-34 We therefore assessed the effect of bone marrow-derived mononuclear cell transplantation on Matrix metalloproteinase-2 and Matrix metalloproteinase-9 activity by gelatin zymographic analysis. | 17322177:1210, 16847153:1174 | 2 | 2
MMP2 ---> blood vessel development | Regulation | P4 suppressed the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP-9, MMP-2), which are involved in tumor vascular development. | 21695351:7 | 2 | 1
MMP2 ---> Breast Neoplasms | Regulation | MMP-2 and its inducer [NAME] maybe participate in invasion and metastasis of breast cancer., In conclusion, this meta-analysis suggested that MMP-2 -1306 C/T polymorphism may contribute to breast cancer susceptibility., MMP-2 may be a useful target for breast cancer therapy when refinement of MMP inhibitors provides for MMP-specific agents., Our results are highly suggestive that MMP2 plays a role in the development of breast cancer metastases, in particular to the brain., Together our results suggest that MMP-2, -3 and -9 may be involved in the process of metastasis of breast cancer to the brain. <more data available...> | 16004819:10, 21161369:8, 14744781:8, 17505812:10, 16158251:8, 16546677:2, 8411260:15, 9740080:1363, 18373849:1214, 20649976:1248 <more data available...> | 2 | 12
MMP2 ---> vasculogenesis | Regulation | Thus, MMP-2 is selectively required for Endothelial progenitor cell vasculogenesis., [NAME] together, our results support the notion that MMP-2 is necessary not only for angiogenesis but also for vasculogenesis., Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix metalloproteinase are required for mimicry of embryonic vasculogenesis by agressive melanoma., Cooperative interactions of laminin 5 gamma2 chain, matrix metalloproteinase-2, and membrane type-1-matrix/metalloproteinase are required for mimicry of embryonic vasculogenesis by aggressive melanoma. <more data available...> | 19874467:7, 17322177:1234, 16294195:1246, 11522618:100, 20375132:1476, 16847153:1174, 17395877:1072 | 2 | 7
MMP2 ---| endothelial cell proliferation | Regulation | Examples of the “molecular target hypothesis” include inhibition of endothelial cell proliferation by the homocysteine metabolite S-adenosylhomocysteine (35), modulation of neuronal N-methyl-d-aspartic acid-like receptor activity by homocysteine (36), the inhibition of tissue plasminogen activator binding to homocysteinylated annexin II (37), activation of matrix metalloproteinases such as latent MMP-2 by homocysteine (38), and, from our own group, the induction of expression and secretion of monocyte chemoattractant protein-1 and interleukin-8 in human aortic endothelial cells by l-homocysteine but notd-homocysteine (39). | 11592966:1266 | 2 | 1
MMP9 --+> Breast Neoplasms | Regulation | These suggest that the genes of KiSS-1, NF-kappaBp50 and [NAME] could be involved in the progression and metastasis of breast cancer., Together our results suggest that MMP-2, -3 and -9 may be involved in the process of metastasis of breast cancer to the brain., The peptide CTT (CTTHWGFTLC) was identified as a selective inhibitor of MMP-2/9 that inhibits the growth of MDA-MB-435 human breast cancer xenografts., In multivariate analysis, preoperative low serum [NAME] increases the risk of relapse 3.0-fold during the first 10 years of follow-up in primary breast carcinoma. <more data available...> | 18844032:7, 16158251:8, 16546677:2, 15617842:7, 11731079:6, 18451168:100, 14978035:1238, 18373849:1214, 16675452:1352, 15059880:1133 <more data available...> | 2 | 21
MMP9 --+> ICAM1 | Expression | The capacity of the MMP-9 inhibitor to prevent sICAM-1 production may be useful for the development of novel therapeutic approaches relevant to osteoarthritic., The soluble factors they release in its presence arrest the cycle of endothelial cells , inhibit in vitro angiogenesis, negatively modulate the production of matrix metalloproteinase-9, and the ability of endothelial cells to adhere to vitronectin and up-regulate ICAM-1 and VCAM-1 expression., These results strongly support our premise that [NAME] promotes angiogenesis by regulating the production of proangiogenic factors such as VEGF and ICAM-1. | 17161959:12, 11238633:3, 15289337:1246 | 2 | 3
MMP9 --+> vascularization | Regulation | [NAME] may be a potential target to disrupt tumor neovascularization., Human gelatinase B is involved in tissue remodeling and angiogenesis., Matrix metalloproteinase-9 (MMP9) plays an important role during angiogenesis., [NAME] expression correlated with B symptoms and decreased new vessel formation., It has been recently found that [NAME] also plays a role in tumor angiogenesis., Matrix metalloproteinase-9 ([NAME]) plays a crucial role in both angiogenesis and tumor invasion., Matrix metalloproteinase-9 ([NAME]) plays important roles in tumor invasion and angiogenesis. <more data available...> | 20873997:2, 9479001:0, 14624478:0, 12431239:2, 15025968:1, 12851530:0, 11781819:0, 12393846:6, 18559512:11, 19016770:3 <more data available...> | 2 | 112
MMP9 ---> arteriogenesis | Regulation | Matrix metalloproteinases have been shown to mediate nitric oxide-induced cadherin/ß-catenin dissociation.29,30 In addition, at least 2 members of the Matrix metalloproteinases family, Matrix metalloproteinase-2 (72 kDa) and Matrix metalloproteinase-9 (92 kDa), play an essential role in vasculogenesis, angiogenesis, and arteriogenesis, 3 processes critical to restoration of tissue perfusion after ischemia.31-34 We therefore assessed the effect of bone marrow-derived mononuclear cell transplantation on Matrix metalloproteinase-2 and Matrix metalloproteinase-9 activity by gelatin zymographic analysis. | 16847153:1174 | 2 | 1
MMP9 ---> blood vessel development | Regulation | P4 suppressed the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMP-9, MMP-2), which are involved in tumor vascular development. | 21695351:7 | 2 | 1
MMP9 ---> endothelial cell proliferation | Regulation | MMP-9 inhibitor GM6001 significantly decreases human cerebral endothelial cell proliferation and migration (p<0.05), indicating the crucial function of MMP-9 in promoting angiogenic changes in human cerebral endothelial cells., Thus treatment with [NAME] decreases endothelial cell proliferation in vitro., [NAME] et al obtained results where type IV gelatinase activity correlated with cancer metastasis.96 Endothelial cell proliferation and migration into the tumor tissue are mediated by angiogenic (eg, Matrix metalloproteinase-9, VEGF, and basic fibroblast growth factor [bFGF]) and lymphangiogenic factors that are released by tumor cells. | 16516857:6, 11803470:1111, 16609063:1129 | 2 | 3
MMP9 ---> ITG | Regulation | Mice in which the integrin-binding motif was mutated to an integrin-disrupting motif (Fbln5RGE/RGE) exhibited upregulation of MMP-9 in vaginal tissues., To evaluate the potential contribution of [NAME] to E-cadherin cleavage, [NAME] was induced in the presence of a MMP-9 function blocking antibody., Among these IVIG-mediated mechanisms may be the suppression of TNF-a (also induced by PMA)19 and the binding of F(ab)2 specifically to RGD (Arg-Gly-Asp) sequences,20 which are necessary for the activity of specific integrins (such as ß1 and ß3) implicated in the expression of MMP-9.16 . <more data available...> | 21519142:4, 17332331:1236, 12404299:1239, 20519536:1320, 18174366:1213 | 2 | 5
MMP9 ---> ITGB1 | Expression | Taken together, our results indicate that [NAME] inhibition induces apoptosis due to altered [NAME]-integrin expression in medulloblastoma., [NAME], spinal administration of exogenous MMP-9 induces morphine withdrawal-like behavioral signs and mechanical allodynia, activates NR1 and NR2 receptors, and downregulates [NAME], while a function-neutralizing antibody against [NAME] suppresses [NAME]-induced phosphorylation of NR1 and NR2B., [NAME] transcriptional suppression decreased the expression of FAK, phospho FAK and [NAME] in glioma xenograft cells. | 17991734:7, 20519536:6, 21855630:6 | 2 | 3
MMP9 ---> NOTCH1 | Regulation | MMP-9 mediates Notch1 signaling via p53 to regulate apoptosis, cell cycle arrest, and inflammation. | 21723221:10 | 2 | 1
MMP9 ---> vasculogenesis | Regulation | Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow-derived myelomonocytic cells., Matrix metalloproteinase-9 is required for tumor vasculogenesis but not for angiogenesis: role of bone marrow- derived myelomonocytic cells., These data provided ex vivo evidence that deficiency of MMP-9 activity impairs microvessel formation and the vasculogenesis ability of endothelial progenitor cells., Matrix metalloproteinases have been shown to mediate nitric oxide-induced cadherin/ß-catenin dissociation.29,30 In addition, at least 2 members of the Matrix metalloproteinases family, Matrix metalloproteinase-2 (72 kDa) and Matrix metalloproteinase-9 (92 kDa), play an essential role in vasculogenesis, angiogenesis, and arteriogenesis, 3 processes critical to restoration of tissue perfusion after ischemia.31-34 We therefore assessed the effect of bone marrow-derived mononuclear cell transplantation on Matrix metalloproteinase-2 and Matrix metalloproteinase-9 activity by gelatin zymographic analysis. <more data available...> | 18328424:100, 20592171:1576, 21258010:1502, 19790065:1573, 19461050:1123, 16847153:1174, 17395877:1072 | 2 | 7
Notch --+> Breast Neoplasms | Regulation | The Notch pathway is dysregulated in human breast tumors and overexpression of constitutively active Notch proteins induces mammary tumors in mice. | 21666715:4 | 2 | 1
Notch ---> blood vessel development | Regulation | Functionally, Notch receptors and ligands are necessary for vascular development., A number of data indicate that appropriate temporal activation of Notch receptors is required for proper vascular development and angiogenesis., hypoxia-inducible factor and Notch family members are critical for proper vascular development, especially during endothelial remodeling, and both families are tightly regulated by ubiquitin-mediated proteasomal degradation., Our analyses of Dll4Lz/+ mice add to a growing body of evidence that indicates that the Notch receptors and their ligands play critical roles during embryonic vascular development, and perhaps in vascular maintenance in the adult as well as during tumor angiogenesis (13, 14). | 15187023:1055, 15044497:1275, 17636018:1302, 15520367:1149 | 2 | 4
Notch ---> Breast Neoplasms | Regulation | Aberrant activation of Notch receptors has been shown to cause mammary tumors in mice., Members of the Notch family are involved in the development of breast cancer in animal models and in humans., However, it is currently not known which, if any, of the NOTCH receptors are involved in the development of ErbB2-negative breast cancers. | 16166334:0, 20562911:0, 18339869:1067 | 2 | 3
Notch ---> endothelial cell proliferation | Regulation | Notch1 is also expressed on endothelial cells, and our data support the notion of a redundancy of function of Notch4 and Notch1 by demonstrating that both members of the Notch family regulate endothelial cell proliferation via a mechanism that converges on inhibition of retinoblastoma protein phosphorylation (15). | 15456857:1302 | 2 | 1
Notch ---> vascularization | Regulation | Recent data indicate that Notch receptors also play a role in tumor angiogenesis., A number of data indicate that appropriate temporal activation of Notch receptors is required for proper vascular development and angiogenesis., Alternatively, arteries in Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy patients may be developmentally altered, because [NAME] family genes are involved in angiogenesis.24 . | 18559519:1078, 15044497:1275, 15017012:1146 | 2 | 3
Notch ---> vasculogenesis | Regulation | The Notch family of receptors and ligands plays an important role in cell fate determination, vasculogenesis, and organogenesis., Normal vasculogenesis is required for normal differentiation of type I from type II pneumocytes, and the [NAME] family is important in embryonic vasculogenesis. | 12456485:0, 12673204:1119 | 2 | 2
NOTCH1 --+> arteriogenesis | Regulation | Notch signaling activity regulates arteriogenesis., Notch signaling plays an important role in the arteriogenesis., Thus, Dll1-mediated Notch activation regulates ephrin-B2 expression and postnatal arteriogenesis., Notch controls arteriogenesis in the adult., Therefore, [NAME] increases Notch1 expression and activity, which may regulate arteriogenesis., Thus Notch1/[NAME] may have a particularly important role in arteriogenesis. *., [NAME]-induced angiogenesis and arteriogenesis is mediated by Notch1 in a murine hindlimb ischemia model without induction of VEGF. <more data available...> | 18927449:0, 20026381:0, 17234965:7, 17938237:1146, 19223914:1211, 16778118:1192, 21301413:100, 18591437:1195 | 2 | 8
NOTCH1 --+> Breast Neoplasms | Regulation | The Numb-mediated regulation of Notch is believed to play a causative role in naturally occurring breast cancers., Combined inhibition of Notch and estrogen signaling has synergistic effects in ERalpha-positive breast cancer models., Recently, a Notch/Myc relationship in oncogenesis was revealed from a mouse model, in which mammary tumors are induced by the intracellular domain of Notch1 ([NAME]))., [NAME], constitutively active mutant forms of the Notch receptor appear to be involved in human T-cell leukemia, mammary carcinomas in mice, and a tumorous germline phenotype in C. elegans. <more data available...> | 17332928:4, 19838210:3, 17329972:1, 10980592:2, 19219656:0, 16947085:2, 15288259:4, 18836481:6, 16751266:1, 18593923:1070 <more data available...> | 2 | 35
NOTCH1 --+> MMP2 | Expression | Hypoxia-induced Notch1 activation increased the expression of matrix metalloproteinase-2 (MMP2) and [NAME], which increased invasiveness. | 23289374:10 | 2 | 1
NOTCH1 --+> MMP9 | Expression | Enforced expression of the cleaved Notch1 in macrophages induces the expression of COX-2 and MMP-9., Down-regulation of Notch-1 also decreased not only MMP-9 mRNA and its protein expression but also inactivated the pro-MMP-9 protein to its active form., We demonstrate that Notch mediates VEGF-induced matrix metalloprotease activity via induction of MMP9 and [NAME] metalloprotease expression and activation of MMP2., Our data show the involvement of Notch1 in human prostate cancer invasion and that silencing of Notch1 inhibits invasion of human prostate cancer cells by inhibiting the expression of MMP9 and [NAME]. <more data available...> | 19290049:5, 16510599:5, 21349159:6, 19147749:10, 19771395:7, 20147635:1271, 19710690:1416, 23289374:10 | 2 | 8
NOTCH1 --+> VEGFA | Expression | Consistent with these results, we found that the down-regulation of Notch-1 reduced nuclear factor-kappaB DNA-binding activity and VEGF expression., Abnormally low expression of Notch1 in esophageal squamous cell carcinoma may be one of the upstream factors to induce high expression of VEGF and increased microvessel density., Notch processing by gamma-secretase results in cleavage of the notch intracellular domain that travels to the nucleus to regulate expression of genes such as vascular endothelial cell growth factor and NFkappaB that are critical in endothelial cell functioning. <more data available...> | 16510599:4, 19923082:7, 18302767:3, 19339510:1198, 19508709:1304, 20522599:1136, 20668292:1055, 18299578:1180, 21731759:100, 23067214:7 | 2 | 10
NOTCH1 ---> blood vessel development | Regulation | Notch signaling plays a key role in embryonic vascular development and angiogenesis., Notch signaling plays an essential role in vascular development and human vascular diseases., To examine the molecular mechanisms by which Notch regulates vascular development, we analyzed changes in gene expression in response to Notch signaling., Notch and transforming growth factor-beta (TGFbeta) play pivotal roles during vascular development and the pathogenesis of vascular disease., Given that Notch signaling plays a crucial role in vascular development, Notch may derive its function via HERP family members. <more data available...> | 20737536:0, 19673359:0, 12814948:2, 20368328:0, 11741889:11, 16697642:2, 17948123:7, 18256896:2, 17556669:1075, 12242716:1193 <more data available...> | 2 | 26
NOTCH1 ---> MMP2 | Regulation | We demonstrate that Notch mediates VEGF-induced matrix metalloprotease activity via induction of MMP9 and [NAME] metalloprotease expression and activation of MMP2., This might be the result of activation of oncogenes or loss of tumor suppressors; for example, MMP-2, MMP-7, or [NAME] is upregulated through combined activation of the transcription factors PEA3, Ets-1, c-Jun, ß-catenin, LEF-1, MEK5, and Notch1, and the transcription of MMP-1 and MMP-13 is repressed by the tumor suppressor p53 (12-14)., Since Notch intracellular domain affects the protein level, TGFß-induced phosphorylation, and nuclear localization of receptor-activated Smads, we next examined the functional effects of Notch intracellular domain on the expression of TGFß target genes. Quantitative Reverse Transcription-PCR showed that activated Notch significantly reduced the basal and TGFß-induced levels of ALK1/Smad1 target genes SMAD6, ID1, and ID2 (Fig. 2A), and two ALK5/Smad2-dependent targets, MMP2 and NET1 (29, 30) ([NAME]. 2B). [FIGURE 2.] View larger version: In this window. <more data available...> | 21349159:6, 19934312:1064, 19473992:1130, 19473993:1130, 22490851:9 | 2 | 5
NOTCH1 ---> vascularization | Regulation | Notch is a critical regulator of angiogenesis and arterial specification., Notch signaling plays a key role in embryonic vascular development and angiogenesis., The transcription factors hypoxia-inducible factor-1alpha and Notch are key regulators of angiogenesis., Inhibition of Notch signalling attenuated visfatin-induced angiogenesis in vitro, ex vivo, and in vivo., Dll4/Notch interaction is essential for proper reparative angiogenesis., Notch1 regulates binary cell fate determination and is critical for angiogenesis and cardiovascular development. <more data available...> | 20298529:0, 20737536:0, 17885420:1, 20817637:1, 20508179:12, 19433762:0, 20624122:3, 18289013:2, 21443520:6, 21533193:3 <more data available...> | 2 | 56
NOTCH1 ---> vasculogenesis | Regulation | Regulation of vascular morphogenesis by Notch signaling., Notch intracellular domain1 or Notch intracellular domain4 overexpression in cultured endothelial cells either inhibits (39, 45) or promotes (41, 64, 69) vascular morphogenesis., The Notch gene family encodes large transmembrane receptors and may regulate embry- onic cell migration, vascular morphogenesis and [NAME] from neuropathology and epidemiology suggests a significant proportion of schizophrenia cases have neurodevelopmental aetiology.4 Additionally, the 6p21-6p23 region has previously been implicated by linkage studies.2 We have attempted to replicate the finding using two Han Chinese samples: (a) 544 cases and 621 controls; and (b) 327 trios. | 17938237:100, 21301413:1288, 19546852:1262, 17220278:1055, 11803454:1053 | 2 | 5
NOTCH1 ---> VEGFC | Regulation | Notch via its induction of VEGFR-3 mediates VEGF-C induced endothelial cell survival and morphological changes. | 17948123:1277 | 2 | 1
NOTCH1 ---| endothelial cell proliferation | Regulation | Moreover, Notch1 mediates VEGF-induced endothelial cell proliferation and migration (35)., We found that Notch1 contributes to VEGF-induced endothelial cell proliferation, migration, and survival., Dll4/Notch signaling in turn attenuates VEGF signaling, thus arresting endothelial cell proliferation, followed by recruitment of mural cells and vessel maturation [7-9,11,12]., The activation of Notch signaling by Jagged1 inhibited Human umbilical vein endothelial cells and human aortic endothelial cell proliferation, whereas [NAME] induced network formation in vitro (40). <more data available...> | 17720887:1254, 17158336:1202, 21092311:1065, 16951162:1343, 17556669:1256, 17090652:1262, 16141350:1212 | 2 | 7
NOTCH1 ---| vascularization | Regulation | Notch is a critical regulator of angiogenesis, vascular differentiation, and vascular integrity., Notch promotes cell survival, angiogenesis and treatment resistance in numerous cancers, making it a promising target for cancer therapy., We have tested both an agonist and antagonist of Notch signaling to study the effects of Notch-mediated angiogenesis on spinal cord vascular pathology following traumatic injury., In these studies, Notch activity seems to participate in cancer metastasis by modulating the epithelial-mesenchymal transition, tumor angiogenesis processes, and the anoikis-resistance of tumor cells. <more data available...> | 21795743:0, 22399357:1, 21156172:1, 22399348:6, 22010178:14, 22858860:0, 22275240:11, 21822553:0, 22848434:0, 22866202:7 <more data available...> | 2 | 13
NOTCH2 ---> blood vessel development | Regulation | Together, these findings infer that Notch2 and Notch3 act together to govern vascular development and smooth muscle differentiation. | 22615991:3 | 2 | 1
NOTCH2 ---> Breast Neoplasms | Regulation | Therefore, Notch-1 may possess tumour-promoting functions, while Notch-2 could play a tumour-suppressive role in human breast cancer., NOTCH1 may thus have tumor-promoting functions, whereas NOTCH2 could have a tumor-suppressive role in human breast cancer, supporting the suppression of NOTCH-1 activity as a therapeutic strategy., Our Quantitative real time-polymerase chain reaction analysis obtained the similar result that Notch2 and ß-catenin were expressed at higher levels in mammosphere cells than in monolayer cells, suggesting that Notch2 and ß-catenin are involved in breast cancer stem cell regulation. | 15492845:8, 17409286:1626, 20569497:1216 | 2 | 3
NOTCH2 ---> vasculogenesis | Regulation | Approximately 25% of these glomeruli have distinct aneurisms instead of capillary tufts.35 Notch2 hypomorphic mice also display generalized edema, although it is not clear whether this is a consequence of a role for Notch2 in lymphatics or a result of its effects in the heart.35 Together these findings indicate that Notch2 is critical for the vascular morphogenesis of a more selective group of vascular beds. | 17556669:1116 | 2 | 1
NOTCH2 ---| MMP9 | Regulation | Down-regulation of Notch2 by small interfering RNA enhanced tumor cell invasion (100.00% ± 21.64% vs 162.22% ± 16.84%, P < 0.05) and expression of MMP9 (1.56 fold, P < 0.05), and activated the pro-MMP9 protein to its active form (1.48 fold, P < 0.05). | 23326131:8 | 2 | 1
NOTCH3 --+> Breast Neoplasms | Regulation | Overexpression of activated Notch-1 and Notch-3 has been shown to induce mammary tumor formation in mice (52)., We believe that NOTCH3 may have all of the properties of lineage-specific oncogenes in breast cancer., Overexpression of activated murine Notch1 and Notch3 in transgenic mice blocks mammary gland development and induces mammary tumors., A recent study further shows that overexpression of activated Notch1 and Notch3 in transgenic mice blocks mammary gland development and induces mouse breast tumors (11). <more data available...> | 17638894:1386, 18339869:1270, 16507912:100, 17332312:1085, 18060036:1227, 22396495:0 | 2 | 6
NOTCH3 --+> vascularization | Regulation | These results provide compelling evidence that Notch3 is important for the investment of mural cells and is a critical regulator of developmental and pathological blood vessel formation., These results convincingly demonstrate that NOTCH3 has a role in fibroblast-mediated angiogenesis. *. | 20689064:9, 19150886:1195 | 2 | 2
NOTCH3 ---> blood vessel development | Regulation | Notch3 plays a role in vascular development and its expression is largely confined to vascular smooth muscle cells in adulthood (22)., These observations signify that Notch3 might have a unique role in modulating vascular development under pathological conditions. [Figure 8] View larger version (37K): [in this window] [in a new window] ., CADASIL is a result of a variety of mutations in the NOTCH3 gene, which is responsible for cell signaling and vascular development.6 A number of polymorphisms in the NOTCH 3 gene have been identified. <more data available...> | 15867348:1236, 20689064:1218, 12574530:1067, 22615991:3 | 2 | 4
NOTCH4 --+> Breast Neoplasms | Regulation | Constitutive activation of Notch-1 (12, 13) or Notch-4 (11) causes mammary carcinogenesis in mice., In this model, induction of mammary tumors by activated Notch4 would be at the low end of the signaling gradient., This particular alteration has been proposed to be important for Notch4's ability to induce mammary tumors in mice., A mouse transgenic model of activated Notch4-driven breast cancer indicates that these tumors are highly metastatic (3)., B, Integration of the MMTV between the LIN12/Notch repeats and the transmembrane domain of the Notch1 or Notch4 gene cause mammary tumors in the mouse.. <more data available...> | 18593923:1070, 15531924:1156, 14762442:1152, 17984306:1261, 17409286:1579, 20068161:1269, 18671830:1243 | 2 | 7
NOTCH4 --+> endothelial cell activation | Regulation | Impaired Notch4 activity elicits endothelial cell activation and apoptosis: implication for transplant arteriosclerosis. | 18802018:100 | 2 | 1
NOTCH4 --+> MMP2 | Expression | Nelfinavir affects Notch 4 processing that results in induction of expression of the pro-angiogenic genes NFkappaB and matrix metalloproteinase 2 in cerebral endothelial cells. | 18302767:10 | 2 | 1
NOTCH4 ---> vasculogenesis | Regulation | Additional receptors, including Notch-4 (40) and ephrins (41) are important regulators of vasculogenesis and angiogenesis. | 11827993:1318 | 2 | 1
NOTCH4 ---| blood vessel development | Regulation | In contrast, increased expression of Notch4 impairs vascular development, as is evident in mice harboring a transgene for an activated form of Notch4 (8)., This phenotype is more severe than that of Notch1 mutants alone, suggesting that Notch1 and Notch4 have partially redundant roles during embryonic vascular development., Although the last two studies demonstrate that both increases and decreases in Notch4 signaling result in a common vascular phenotype, disrupted blood vessel development, a mechanism(s) by which to explain this phenotype has not been elucidated. <more data available...> | 14672936:1217, 17409286:1338, 11909975:1381, 19812212:1060, 17185616:1063 | 2 | 5
NOTCH4 ---| vascularization | Regulation | Based on the function of other Notch family members and the expression pattern of Notch4, we postulated that Notch4 activation would modulate angiogenesis., Among them Notch1/4, Hey1/2, [NAME] and RBPJkappa have been shown to be crucial for fetal angiogenesis, Notch2 is necessary for formation of maternal blood vessels in the placenta and [NAME] is indispensable for proper trophoblast cell type specification., Activated Notch4 inhibits angiogenesis: role of beta 1-integrin activation., Additional receptors, including Notch-4 (40) and ephrins (41) are important regulators of vasculogenesis and angiogenesis. <more data available...> | 11909975:3, 18603295:4, 17279577:1818, 11827993:1318, 15044497:1279, 15456857:1146, 14528285:1134, 12482957:1131, 19218547:1054, 17054791:1375 <more data available...> | 2 | 12
VEGFA --+> arteriogenesis | Regulation | In vitro experiments suggest that nerve-derived VEGF may be important for arteriogenesis, but its role in vivo remains unclear., However, when co-delivered with VEGF, TERTdn abrogated VEGF-dependent angiogenesis, arteriogenesis, and blood flow increase., The negative effects of smoking on monocyte function may translate into adverse impacts on VEGF-A-dependent repair processes such as arteriogenesis., These data imply that the activation of both monocytes and endothelial cells is necessary to obtain a maximal VEGF-induced activation of arteriogenesis. <more data available...> | 15673567:1, 15687494:5, 17053168:10, 14985076:9, 17885189:11, 16188064:14, 15916974:1, 18802023:3, 12810080:0, 12714562:6 <more data available...> | 2 | 54
VEGFA --+> blood vessel development | Regulation | Vascular endothelial growth factor (VEGF) is known to play an essential role in vascular development., Vascular permeability factor (VPF) is an important mediator of vascular development in tumors., Vascular endothelial growth factor (VEGF) is an important mediator of vascular development in tumors., Vascular endothelial growth factor (VEGF)-A regulates vascular development and angiogenesis., Vascular endothelial growth factor (VEGF) is known to play an essential role in embryonic vascular development., The vascular endothelial growth factors VEGFA and VEGFC are crucial regulators of vascular development. <more data available...> | 16630570:0, 8644861:0, 9646228:0, 18664627:0, 10888256:0, 20224550:0, 11169844:6, 15557114:0, 12617854:3, 14516677:3 <more data available...> | 2 | 107
VEGFA --+> Breast Neoplasms | Regulation | Due to it the VEGF seems to be an optimal therapeutic target in breast cancer therapy., VEGF might be a potential therapeutic target for human breast cancer., Her-2 and VEGF may play synergic roles in the occurrence and development of breast cancer., Vascular endothelial growth factor (VEGF) is recognized to play a predominant role in breast cancer prognosis., The angiogenic factor vascular endothelial growth factor (VEGF)-A plays an important role in breast cancer progression., Results from our study indicate that common genetic variation in VEGFA and [NAME] (VEGFR1) may contribute to breast cancer susceptibility. <more data available...> | 19227609:2, 19162240:7, 20868598:6, 10604730:0, 12115372:0, 21119072:7, 20707740:12, 18079435:0, 14613032:0, 11866906:9 <more data available...> | 2 | 73
VEGFA --+> endothelial cell activation | Regulation | Prior murine and human studies suggest that vascular endothelial growth factor (VEGF) contributes to endothelial cell activation and severity of illness in sepsis., Formation of a Rap1/Bmx complex was not observed in cells transfected with an expression vector for a dominant-negative Rap1, indicating that Bmx is a downstream Rap1 effector in VEGF-induced endothelial cell activation., Thrombin, vascular endothelial growth factor and interleukin-8 synergistically augment angiogenesis in a milieu of reactive oxygen species-induced endothelial cell activation. <more data available...> | 18598002:0, 15207703:5, 19208784:5, 7566855:0, 9612282:4, 10886518:1039, 19578010:1171, 14654523:1348, 15507525:1167, 17463183:1304 <more data available...> | 2 | 21
VEGFA --+> endothelial cell proliferation | Regulation | VEGF has been shown to regulate endothelial cell proliferation and migration., Blocking led, as expected, to abrogation of VEGF-induced endothelial cell proliferation in vitro., Vascular endothelial growth factor (VEGF) is a potent stimulator of endothelial cell proliferation., [NAME] VEGF165 can stimulate the vascular endothelial cell proliferation., [NAME] VEGF165 can accelerate the vascular endothelial cell proliferation., The vascular endothelial growth factor (VEGF) family is a novel regulator of endothelial cell proliferation. <more data available...> | 18509061:0, 12067896:5, 11158026:0, 15555444:10, 16109517:13, 10487612:0, 20715116:1, 11432658:2, 11895203:0, 18565703:5 <more data available...> | 2 | 125
VEGFA --+> endothelialization | Regulation | VEGF plays the key role in reendothelialization., Moreover, 8 weeks of VPF administration resulted in 88.1 +/- 3.1% re-endothelialization compared to control (44.7 +/- 3.8%)., Moreover, regulation of VEGF by alpha2-AP significantly affected reendothelialization after vascular injury., Vascular endothelial growth factor (VEGF) is highly expressed in vascular remodeling processes and accelerates reendothelialization after mechanical denudation., Conversely, sequestration of exogenous and/or endogenous VEGF by VEGF-trap delayed reendothelialization and significantly increased neointima size. <more data available...> | 11832184:8, 7946409:5, 16515500:7, 10828020:0, 15477421:10, 12538420:9, 11758260:9, 9240325:11, 12123557:8, 12893771:6 <more data available...> | 2 | 53
VEGFA --+> ICAM1 | Expression | VEGF increases retinal vascular ICAM-1 expression., VEGF (20 ng/ml) increased expression of ICAM-1, VCAM-1, and E-selectin mRNAs in a time-dependent manner., In this study, we provided a new mechanism to explain that VEGF does up-regulate the expression of ICAM-1 in retinal ECs., [NAME] inhibited the VEGF-induced protein and mRNA expression of ICAM-1, VCAM-1, and E-selectin., RT-PCR and promoter analysis revealed that HGF downregulated VEGF-mediated expression of ICAM-1 and VCAM-1 at the transcriptional level. <more data available...> | 10393052:8, 11108718:2, 19236815:3, 12805078:4, 15637298:7, 14744874:9, 15579431:5, 10374752:6, 15020646:5, 11839570:12 <more data available...> | 2 | 60
VEGFA --+> ITG | Expression | IL-1beta, expressed by the blastocyst, induces vascular endothelial growth factor (VEGF) which, in turn, promotes angiogenesis and integrin expression in endometrial cells., The authors investigated the regulation of expression of these angiogenic integrins by hypoxia and vascular endothelial growth factor (VEGF) in retinal microvascular endothelial cells in culture., Studies in cultured lymphatic endothelial cells revealed that VEGF-A induced expression of the [NAME] and alpha2 integrins, which promoted their in vitro tube formation and their haptotactic migration toward type I collagen. <more data available...> | 11023800:2, 9579483:1, 15132990:4, 9775530:4, 10924500:1199, 19351819:1157, 17085437:1070, 16980351:1432, 11139149:100, 14996996:1230 <more data available...> | 2 | 18
VEGFA --+> ITGB1 | Expression | Thus, VEGF can modulate angiogenesis via increased expression and activation of alpha(6)beta(1) integrins, which may promote VEGF-driven tumor angiogenesis in vivo., Treatment with anti-VEGF antibody decreases the expression of [NAME], [NAME], DNA-PK(CS) and ATM with a corresponding increase in ionizing radiation -induced apoptosis., CD29 (ß1-integrin) expression was significantly increased by all VEGF isoforms used at 125 ng/ml, most markedly by native VEGF189., VEGF upregulates expression of the a1ß1 and a2ß1 integrins in microvascular endothelial cells. <more data available...> | 17085437:7, 15135073:2, 14968118:1161, 18840653:1249, 16774905:1234, 9391074:1182, 18566344:1309 | 2 | 7
VEGFA --+> MMP2 | Expression | The expression of MMP-2 was increased as early as 1 hour post VEGF treatment., VEGF-induced MMP-2 mRNA expression was reduced by inhibition of JNK or by treatment with c-Jun siRNA., VEGF can upregulate the expression of MMP-2, [NAME] in HL-60 and a part of the primary leukemic cells., [NAME] and protein were significantly increased during VEGF165 cDNA transfection; MMP-2 activity was also increased., Zymography and Western blot analyses demonstrated that gelatinase A levels in the media were increased by VEGF treatment. <more data available...> | 20635039:13, 16672691:8, 16584583:10, 16525667:6, 9473407:3, 19306293:4, 16369727:10, 19763043:4, 12133405:4, 19068239:6 <more data available...> | 2 | 33
VEGFA --+> MMP9 | Expression | The hypoxic expression of MMP-9 was mediated by autocrine VEGF signaling., [NAME], but not MMP-2, mRNA was increased during VEGF stimulation., VEGF can upregulate the expression of MMP-2, [NAME] in HL-60 and a part of the primary leukemic cells., It is possible that upregulation of HIF-1/VEGF is involved in the enhancement of MMP-9 expression under hypoxic conditions., Vascular endothelial growth factor (VEGF) has been shown to up-regulate the expression of MMP-9 in vascular smooth muscle cells., These findings suggest that VEGF signaling regulates [NAME] expression and plays a critical role in initiation and maintenance of asthma. <more data available...> | 17724228:9, 15256478:5, 16584583:10, 20631454:8, 12851530:1, 16645174:7, 10953026:5, 9776730:5, 18403633:9, 21349159:6 <more data available...> | 2 | 40
VEGFA --+> Notch | Expression | VEGF is upregulated in response to hypoxia11 and promotes angiogenesis in ischemic tissues.12 Although VEGF also increases the expression of Notch receptors and their ligands, it is not known whether Notch receptors are necessary for VEGF-mediated angiogenic response.13 The purpose of this study was to determine whether [NAME] are essential for postnatal angiogenesis and, if so, to determine the signaling pathway(s) that leads to Notch cleavage and signaling in vascular endothelial cells. *. | 17158336:1060 | 2 | 1
VEGFA --+> NOTCH1 | Expression | For arterial specification, vascular endothelial growth factor (VEGF) induces expression of Notch signaling genes, including Notch1 and its ligand, Delta-like 4 ([NAME]), and Foxc1 and Foxc2 transcription factors directly regulate [NAME] expression., This down-regulation of VEGF in preeclamptic placentas, in turn, probably decreases Notch protein expression in placental compartments and in endothelial cells and could offer an ethiopathogenetic explanation for the onset of this pathology., Treatment of endothelial cells with VEGF increases presenilin proteolytic processing, gamma-secretase activity, Notch1 cleavage, and Hes-1 (hairy enhancer of split homolog-1) expression, all of which were blocked by treating endothelial cells with inhibitors of phosphatidylinositol 3-kinase/protein kinase [NAME] or infecting endothelial cells with a dominant-negative [NAME] mutant. <more data available...> | 20238301:1, 17955263:10, 17158336:4, 18827808:1150, 20436223:100, 12482957:1174, 19097050:1223, 12865906:1124, 18093989:1225, 17376817:1254 <more data available...> | 2 | 17
VEGFA --+> NOTCH4 | Expression | Overexpression of VEGF-induced Notch4 and the Notch ligand, [NAME], activated Notch signaling, and altered endothelial cell morphology in a fashion similar to that induced by Notch activation., In venous endothelial cells, we showed that VEGF up-regulates [NAME] and presenilin, and increased the activation of Notch4, leading to an up-regulation of ephrin B2 with a down-regulation of Eph B4., This underscores that VEGF signalling in venous ECs might induce expression of arterial markers, such as Notch1 and Notch4. <more data available...> | 21349159:4, 16951162:5, 18093989:1225, 17220278:1062, 17185616:1216 | 2 | 5
VEGFA --+> vascularization | Regulation | VEGF165 induces marked vascular growth., VEGF is a major inducer of angiogenesis., VEGF is an important factor for angiogenesis., VEGF-A promotes angiogenesis in many tissues., VEGF and HIF-1 are potent inducers of angiogenesis., VEGF plays a central role in tumor angiogenesis., [NAME] inhibits VEGF-induced neovascularization., VEGF plays a principal role in tumor angiogenesis., VEGF was an important factor in tumor angiogenesis., VEGF-A is the essential factor in tumor angiogenesis. <more data available...> | 1384392:3, 19800880:0, 14717227:0, 16453023:0, 18288940:6, 17615535:3, 18484196:2, 15064856:2, 12500403:10, 18282597:1 <more data available...> | 2 | 547
VEGFA --+> vasculogenesis | Regulation | Vascular endothelial growth factor (VEGF) is a regulator of vasculogenesis and angiogenesis., Vascular endothelial growth factor (VEGF) plays an important role in early embryonic vasculogenesis., Recent evidence indicates that VEGF is essential for embryonic vasculogenesis and angiogenesis., Vascular endothelial growth factor (VEGF) is a major inducer of angiogenesis and vasculogenesis., Vascular endothelial growth factor (VEGF) is a principal regulator of vasculogenesis and angiogenesis., Vascular endothelial growth factor (VEGF) is an important regulator of vasculogenesis and angiogenesis. <more data available...> | 9399960:0, 10340756:0, 10494799:1, 14987558:0, 10815805:0, 11494124:0, 14986821:0, 12058259:0, 15814647:1, 11245271:0 <more data available...> | 2 | 108
VEGFB --+> arteriogenesis | Regulation | The VEGF-B transgene induces strong arteriogenesis in rat myocardium., VEGFR-1 mediated biological functions remain undetermined although early reports suggest that VEGF-B [57] and PlGF [58] may induce angiogenesis, arteriogenesis and vasculogenesis., While one study reported smaller heart and abnormal coronary artery vasculature caused by VEGF-B deficiency in mice (17), this was not observed in another independent study (16)., Vascular endothelial growth factor-B induces myocardium-specific angiogenesis and arteriogenesis via vascular endothelial growth factor receptor-1- and [NAME] receptor-1-dependent mechanisms. <more data available...> | 20937974:1134, 15664390:1146, 18259607:1061, 19188502:100, 16109918:1277 | 2 | 5
VEGFB --+> endothelial cell proliferation | Regulation | Vascular endothelial growth factor-B is therefore unlikely to promote endothelial cell proliferation or migration directly. | 12942123:1191 | 2 | 1
VEGFB --+> vascularization | Regulation | VEGF-B, but not [NAME], caused angiogenesis in the tibialis anterior muscle., Its correlation with VEGF, b-FGF, and mean vessel density potentiates its possible role in angiogenesis., Vascular endothelial growth factors A and B (VEGF-A and VEGF-B) play a major role in angiogenesis and activate VEGF receptor 1 (VEGFR-1)., VEGF-A and VEGF-B play major roles in angiogenesis as ligands of tyrosine activity receptors: VEGFR-1 and VEGFR-2., Among the vascular endothelial growth factors, VEGF-A and VEGF-B predominantly induce angiogenesis while VEGF-C and VEGF-D induce lymphangiogenesis. <more data available...> | 18552506:11, 10443829:10, 17150246:0, 16967703:5, 18479712:1, 9426398:7, 12805240:11, 14713119:9, 18511699:2, 19684473:1 <more data available...> | 2 | 52
VEGFB --+> vasculogenesis | Regulation | VEGFR-1 mediated biological functions remain undetermined although early reports suggest that VEGF-B [57] and PlGF [58] may induce angiogenesis, arteriogenesis and vasculogenesis., This raises the question of whether VEGF-B is truly angiogenic, as suggested in previous in vivo studies, or whether VEGF-B may have promoted vessel growth by vasculogenesis through mobilization/recruitment of EPCs. | 15664390:1146, 16109918:1269 | 2 | 2
VEGFB ---> ICAM1 | Regulation | B, time-response curve of ICAM-1 regulation by basic fibroblast growth factor, VEGF-A, VEGF-B, and VEGF-C, as measured by flow cytometry. -[?]´-, basic fibroblast growth factor; -[?]¾-, VEFG-A; -?-, VEGF-C; -•-, VEFG-D. | 15534089:1198 | 2 | 1
VEGFC --+> Breast Neoplasms | Regulation | VEGF-C, COX-2, and lymph vessel density play important roles in the lymphatic metastasis of breast cancer., In conclusion, these results indicate that lentivirus-mediated VEGF-C small interfering RNAs offers a new approach for therapeutic intervention to prevent tumor growth and lymphatic metastasis of breast cancer., Activation of VEGF-C/VEGF-D/VEGFR-3 axis increases motility and invasiveness of neoplastic cells, promotes development of metastases in several types of tumours such as, e.g., lung cancer, mammary carcinoma, cancers of the neck, prostate and large intestine. <more data available...> | 18353210:4, 19382240:12, 20164015:6, 12692195:1126, 16204074:1195, 18923001:1194, 20179201:1055, 20179202:1055, 17912247:1188, 12782611:1104 <more data available...> | 2 | 13
VEGFC --+> endothelial cell proliferation | Regulation | VEGF-C secreted by PANC-1 cells stimulated human lymphatic endothelial cell proliferation., soft-tissue sarcoma cells secreted functional VEGF-C: soft-tissue sarcoma conditioned medium induced lymphatic endothelial cell proliferation and migration, which was abrogated by soft-tissue sarcoma cell VEGF-C knockdown., These results suggest that whereas excess VEGF-C may enhance early lymphatic endothelial cell proliferation and cause lymphatic vessel hyperplasia, it does not augment the physiological rate of migration or functionality, and by itself cannot sustain any lasting effects on lymphatic size, density, or organization in regenerating adult skin. <more data available...> | 19719950:6, 19351758:7, 15890974:7, 12388793:100, 11282897:1152, 11297234:1089, 20689828:1491, [NAME], 9826710:1185, 17210781:1198 <more data available...> | 2 | 19
VEGFC --+> endothelialization | Regulation | VEGF-C application reduced neointima formation and accelerated reendothelialization., Indeed, reports in animal models demonstrate that local administration of VEGF-A or VEGF-C leads to accelerated reendothelialization and a reduction in intimal thickening.2-5 ., VEGF-C has been shown to be angiogenic in the rabbit ischemic hindlimb model,104 and our recent unpublished data show that VEGF-C gene transfer can accelerate reendothelialization and inhibit intimal hyperplasia in the balloon-injured rabbit aorta ([NAME], K. Alitalo, [NAME], et al, unpublished data, 1999). | 14769706:6, 15492329:1049, 10845866:1101 | 2 | 3
VEGFC --+> ITG | Regulation | Binding of VEGF-C and -D to a9ß1 activates the integrin. | 15590642:1195 | 2 | 1
VEGFC --+> ITGB1 | Expression | [NAME] was greatly increased at 3 hours by stimulation of 100 ng/ml CXCL12 (before and after stimulation 0.53 +/- 0.10, 1.53 +/- 0.16; P < 0.01), and VEGF-C mRNA showed significant increase at 24 hours by treatment with CXCL12 (before and after stimulation 0.52 +/- 0.09, 1.11 +/- 0.15; P < 0.05). | 17697603:9 | 2 | 1
VEGFC --+> MMP2 | Expression | In contrast, the invasive and gelatinolytic activities of OMC-3 cells with lower gene expression levels of VEGF-C and MMP-2 were stimulated by the presence of 1 to 10 µg/mL VEGF-C in a concentration-dependent manner ([NAME]. 2C and F), respectively. | 15867217:1184 | 2 | 1
VEGFC --+> vascularization | Regulation | VEGF-C may play an important role in the angiogenesis and lymphangiogenesis., [NAME] of VEGF-C also resulted in aberrant blood vessel formation in tadpoles., Vascular endothelial growth factor-C (VEGF-C) and VEGF-A are involved in lymphangiogenesis and angiogenesis., The recombinant VEGF-C induced angiogenesis in the chicken chorioallantoic membrane model., In addition to VEGF, c-met seems to be important and clinically relevant to the induction of angiogenesis in prostate cancer., VEGF-C mainly promotes peri-tumor lymphangiogenesis and has a little effect on angiogenesis. <more data available...> | 16859137:12, 16116431:6, 18654613:1, 16159421:7, 15274358:11, 12452004:7, 18061373:11, 9708799:2, 14710191:5, 9826710:2 <more data available...> | 2 | 107
VEGFC --+> vasculogenesis | Regulation | Vascular endothelial growth factor-C promotes vasculogenesis, angiogenesis, and collagen constriction in three-dimensional collagen gels. | 15874936:100 | 2 | 1
VEGFC ---> blood vessel development | Regulation | The vascular endothelial growth factors VEGFA and VEGFC are crucial regulators of vascular development., Vegfc is required for vascular development and endoderm morphogenesis in zebrafish., VEGF-C is essential for embryonic lymphatic vascular development whereas VEGF-D has a dispensable modifier role in this process., It is possible that CLP24 participates also in VEGF-C-mediated blood vascular development in fish and frog embryos, thus explaining the observed vascular defects in the morphants., Recent studies in vivo showed that VEGF-C can promote angiogenesis in rabbit ischemic limbs (36) and [NAME] and blood vessel development in chicken embryo chorioallantoic membrane assay (37). <more data available...> | 20224550:0, 14710191:100, 18725566:1036, 20439428:1156, 10488101:1061, 19423848:1174 | 2 | 6
VEGFC ---> ICAM1 | Regulation | VEGF-C and VEGF-D synergize with basic fibroblast growth factor to down-regulate ICAM-1 on endothelial cells. | 15534089:1194 | 2 | 1
VEGFC ---> vasculogenesis | Regulation | We also demonstrate that Vegfc is required for vasculogenesis as well as angiogenesis in the zebrafish embryo., Vascular endothelial growth factor-C promotes vasculogenesis, angiogenesis, and collagen constriction in three-dimensional collagen gels., Several genes encoding growth factors/secreted molecules, such as apoEb, vegf-c, and granulin-A, were strongly expressed at 3 d postamputation (Figure 2A and 2C) and are likely involved in the wound healing process. vegf-c is required for vasculogenesis and angiogenesis in the zebrafish embryo [13] and may play a role in the wound healing response to heart injury and regeneration. granulin A, a growth factor gene involved in wound response [14], was also strongly upregulated at 3 d postamputation (Figure 2A and 2C). <more data available...> | 14710191:5, 15874936:100, 16869712:1162, 22792354:6 | 2 | 4
VEGFC ---| NOTCH1 | Regulation | Vegfa-Vegfr2 Signal and Vegfc-Vegfr3 Signal Are Required for Abnormal Branching of intersegmental vessels Vegfa-Vegfr2 (Kdr) and Vegfc-Vegfr3 (Flt4) signaling pathways are essential for vascular development in zebrafish and mammals.9,31 In the vascular sprouting, tip cells responding to Vegfa express [NAME], thereby suppressing Vegfr2 and Vegfr3 through Notch signaling in the stalk cells.3 In sarsko095/ko095 mutants, the abnormal branching started after the establishment of intersegmental vessels. | 19423848:1174 | 2 | 1
VEGFR ligand --+> arteriogenesis | Regulation | Several growth factors, including VEGFs, fibroblast growth factors, PDGFs, MCP-1 and GM-CSF, have been shown to induce both angiogenesis and arteriogenesis [7]. | 15664392:1088 | 2 | 1
VEGFR ligand --+> ITG | Regulation | VEGFs and bFGF are well-established activators of endothelial integrin function both in vivo and in vitro.48-52 It has recently been demonstrated that SEMA3F inhibits the mitogenic effects of VEGF-A165 and bFGF on HUVECs.36 Inhibition of bFGF-induced proliferation did not seem to rely on the inhibition of the binding of bFGF to its receptors or on the up-regulation of VEGF or VEGFR-2 expression, as demonstrated previously.53,54 Moreover, SEMA3A inhibited both VEGF-A- and bFGF-enhanced adhesion of endothelial cells to fibronectin. | 16621967:1304 | 2 | 1
VEGFR ligand --+> vascularization | Regulation | The VEGFs and FGF-2 stimulate angiogenesis., Vascular endothelial growth factors are crucial regulators of angiogenesis and vasculogenesis., Vascular endothelial growth factors are key regulators of endothelial cell function and angiogenesis., Vascular endothelial growth factors and their receptors play key roles in angiogenesis and lymphangiogenesis., Vascular endothelial growth factors and their receptors are thought to be involved in normal endometrial angiogenesis., Vascular endothelial growth factors (VEGF) are the major inducers of vasculogenesis and angiogenesis in vertebrates. <more data available...> | 15582590:0, 20603618:0, 21507243:0, 16505489:0, 15760960:2, 15366007:0, 11457758:0, 7515293:4, 19509553:0, 17658244:0 <more data available...> | 2 | 67
VEGFR ligand ---> blood vessel development | Regulation | Vascular endothelial growth factors (VEGF) are potent effectors of vascular development., Vascular endothelial growth factors regulate vascular development, angiogenesis and lymphangiogenesis by binding to a number of receptors., There is now a consensus that the VEGFs are crucial for vascular development and neovascularization in physiological and pathological processes in both embryo and adult., Both VEGFs and ANG2 are required for normal coronary vascular development., In addition to binding secreted semaphorins, neuropilins are coreceptors for vascular endothelial growth factors (Soker et al., 1998[Go]; Gluzman-Poltorak et al., 2000[Go], 2001[Go]; [NAME] et [NAME], 2006[Go]), molecules actively involved in vascular development and recently shown to have roles in neuronal migration (Schwarz et al., 2004[Go]). <more data available...> | 12112468:1, 17658244:0, 13678960:1, 19179669:1156, 17329436:1061, 21711246:0, 22287362:0 | 2 | 7
VEGFR ligand ---> endothelial cell proliferation | Regulation | VEGFs are secreted or cell-bound proteins expressed by tumor cells that function in a paracrine fashion by binding to specific high-affinity transmembrane receptors on endothelial cells (8, 9) to promote endothelial cell proliferation and survival., vascular endothelial growth factors are secreted or cell surface-bound proteins expressed by tumor cells that bind to specific high-affinity transmembrane receptors primarily expressed on endothelial cells (5) to promote endothelial cell proliferation, migration, and survival. <more data available...> | 16299247:1075, 16912155:1066, 16195704:1031, 18836096:1059 | 2 | 4
VEGFR ligand ---> vasculogenesis | Regulation | Vascular endothelial growth factors are crucial regulators of angiogenesis and vasculogenesis., Vascular endothelial growth factors (VEGF) are the major inducers of vasculogenesis and angiogenesis in vertebrates., Vascular endothelial growth factors and their receptors are essential regulators of vasculogenesis and angiogenesis in both embryos and adults., Vascular endothelial growth factors and their endothelial tyrosine kinase receptors are central regulators of vasculogenesis, angiogenesis and lymphangiogenesis. <more data available...> | 20603618:0, 15366007:0, 11457758:0, 19230644:0, 11160848:1, 20565841:1105, 11901186:1053, 18523681:1221, 21937420:1, 22670172:0 | 2 | 10