bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0524PERICYTE IS ESSENTIAL FOR RENAL TUBULAR CELL REGENERATION AFTER ACUTE KIDNEY INJURY
Authors: Chou Yu-Hsiang , SHAO YU-HAN , LIN SHUEI-LIONG 
Published: June 2020

Abstract

Background and Aims
Pericyte-myofibroblast transition is activated after acute kidney injury (AKI) and is the major mechanism of ensuing chronic kidney disease (CKD). Nevertheless, the role of pericyte in renal regeneration after AKI has not been deeply investigated. Many studies have shown that pericyte can secret growth factors such as fibroblast growth factor 1 and 7 (FGF-1, FGF-7) and is essential for structure support and vascular integrity in normal kidney. We supposed that the ablation or inhibition of pericytes during AKI would retard renal repair.

Method
Our study demonstrated that activated pericytes/myofibroblast was beneficial for renal regeneration after AKI. We here performed pericyte ablation and pericyte inhibition after ischemia-reperfusion renal injury by using transgenic mice such as Gli1-CreERT2;iDTR mice and blockade of platelet-derived growth factor receptor β (PDGFRβ), respectively.

Results
Renal injury was more severe and renal recovery was worse in groups of pericyte ablation or inhibition compared to control groups. Ki67 positive tubular cells which indicated renal regeneration were much more in control groups than that in groups of pericyte ablation or inhibition. We also found higher macrophage number as well as higher inflammatory factor including tumor necrosis factor-α and interleukin-1β which indicated more severe inflammation in groups of pericyte ablation or inhibition.

Conclusion
These studies suggest that pericytes play a beneficial role during renal recovery after AKI. These findings delineate the adequate timing when we target on pericyte/myofibroblast to ameliorate renal fibrosis and avoid to impede renal regeneration at the same time. Further research is still needed to clarify the change of specific gene and signalling pathway after pericyte ablation or inhibition. These are promising findings that provide opportunities to develop new targets to promote AKI recovery and to ameliorate renal fibrosis.
P0526MIR-181D-5P TARGETS KLF6 TO IMPROVE ISCHEMIC/REPERFUSION AKI THROUGH EFFECTS ON RENAL FUNCTION,APOPTOSIS AND INFLAMMATION
Authors: Xu Yan , Zhang Yue 
Published: June 2020

Abstract

Background and Aims
Inflammation and renal tubular cell death is the most crucial pathophysiological changes in acute kidney ischemic/reperfusion injury(IRI). The miR-181d family plays diverse roles in cell proliferation, apoptosis and inflammation, but its renal target and potential role in IRI are unknown.

Method
We built hypoxia/reoxygenation (H/R) renal cell model (HK-2 cells) and renal ischemia/reperfusion (I/R) injury mice model. We used observe the expression location of miR-181d-5p and KLF6 by in situ hybridization and immunohistochemistry, the blood creatinine and urea nitrogen levels through fully automatic biochemical detector, the severity of kidney injury by HE staining, the apoptosis and necrosis of renal tubular epithelial cells by TUNEL and Annexin V-FITC/PI flow cytometry, the concentrations of pro-inflammatory factors in the cell supernatant by ELISA and the mRNA and protein levels of related factors and predicted and verified the relationship between miR-181d-5p and KLF6 via bioinformatics systems and luciferase reporter genes.

Results
We showed that the expression of miR-181d-5p decreased in HK-2 cells of H/R and renal mouse model of I/R injury. Mechanistically, KLF6 was predicted as a new potential target gene of miR-181d-5p through bioinformatics and the Luciferase reporter verification. After renal ischemia/ reperfusion, overexpression of microRNA-181d significantly attenuated the level of KLF6 and inhibited inflammatory mediators such as IL-6, TNF-α, reducing apoptosis and further improving renal function. Critical NF-κB signaling pathways mediated this inflammatory response.

Conclusion
In conclusion, upregulation of microRNA-181d inhibits KLF6 expression, which have protective anti-apoptosis and anti-inflammatory effects against I/R kidney in vivo, and H/R HK-2 cells in vitro, thereby providing novel insights into the molecular mechanisms associated with ischemia/reperfusion injury and a potential novel therapeutic target.
P0527HYPERGLYCEMIA-ASSOCIATED ACUTE KIDNEY INJURY INCREASES THE SUSCEPTIBILITY TOWARDS NEUROLOGICAL DYSFUNCTION: ROLE OF ANGIOTENSIN II TYPE 2 RECEPTOR AND ANGIOTENSIN-CONVERTING ENZYME 2
Authors: Sharma Nisha , Gaikwad Anil Bhanudas 
Published: June 2020

Abstract

Background and Aims
In clinical settings, diabetics remain on higher risk of ischemic renal injury (IRI) than nondiabetic patients. In addition, IRI predisposes distant organs to dysfunction such as neurological impairments via activation of the pressor arm of renin-angiotensin system (RAS). In contrast, the role of depressor arm of RAS on IRI-associated neurological sequalae remains elusive. Hence, this study explored the role of angiotensin II type 2 receptor (AT2R) and angiotensin-converting enzyme 2 (ACE2) in IRI-associated neurological dysfunctions under nondiabetic (ND) and diabetes mellitus (DM) condition.

Method
Type 1 diabetes was induced by injecting streptozotocin (55 mg/kg i.p.). ND and DM rats with bilateral IRI were treated with AT2R agonist-Compound 21 (C21) (0.3 mg/kg/day, i.p.) or ACE2 activator-Diminazene Aceturate (Dize), (5 mg/kg/day, p.o.) per se or in combination therapy. Behavioural, biochemical, and histopathological analysis were done to assess IRI-induced neurological impairment. Moreover, immunohistochemistry, ELISA and qRT-PCR experiments were conducted for molecular mechanism analysis.

Result
In ND and DM rats, IRI caused hippocampal complications as evidenced by increased MDA and nitrite levels, augmented inflammatory cytokines (granulocyte colony stimulating factor, glial fibrillary acidic protein), altered protein and mRNA expressions of Ang II, Ang-(1-7), AT1R, AT2R and MasR. In contrast, concomitant therapy of C21 and Dize effectively normalised aforementioned hippocampal alterations. The protective effect of combination therapy was exerted due to augmented protein and mRNA levels of depressor arm components.

Conclusion
The current study demonstrated the protective role of AT2R agonist and ACE2 activator in IRI-associated neurological dysfunction through preventing oxidative stress, inflammation and upregulating brain depressor arm of RAS under ND and DM conditions.
P0527AROLE OF PROMOTING INFLAMMATION OF KLF6 IN ACUTE KIDNEY INURY
Authors: Li Dan , Li Chenyu , Xu Yan 
Published: June 2020

Abstract

Background and Aims
Acute kidney injury (AKI), commonly appeared in cardiac arrest, surgery and kidney transplantation which involved in ischemia-reperfusion (IR) injury of kidney. However, the mechanisms underlying inflammatory response in IR AKI is still unclear.

Method
Public dataset showed kruppel-like factor 6 (KLF6) was significantly highly expressed (P&lt;0.05) in AKI, implies KLF6 might be associated with AKI. To evaluate the mechanism of KLF6 on IR AKI, 30 rats were randomly divided into sham and IR group, and were sacrificed at 0 h, 3 h, 6 h, 12 h or 24 h after IR.

Results
The results showed KLF6 expression was peaking at 6 h after IR, and the expression of pro-inflammatory cytokines MCP-1 and TNF-α were increased both in serum and kidney tissues after IR, while anti-inflammatory cytokine IL-10 was decreased after IR. Furthermore, in vitro results showed KLF6 knock-down reduced the pro-inflammatory cytokines expression and increased the anti-inflammatory cytokines expression.

Conclusion
These results suggest that (1) KLF6 might be a novel biomarker for early diagnosis of AKI and (2) targeting KLF6 expression may offer novel strategies to protect kidneys from IR AKI

Figure
KLF6, AKI, Control Inflammation
P0528RENOPROTECTIVE EFFECT OF IL-34 INHIBITION ON CISPLATIN-INDUCED NEPHROTOXICITY IN MICE
Authors: Wada Yukihiro , Iyoda Masayuki , Matsumoto Kei , Suzuki Taihei , Iseri Ken , Tachibana Shohei , Kanazawa Nobuhiro , Sugiyama Motonori , Honda Hirokazu 
Published: June 2020

Abstract

Background and Aims
Interleukin (IL)-34, a macrophage (Mø) mediator, is expressed by tubular epithelial cells (TECs). However, the influence of IL-34 on TECs injury has not been fully elucidated. We investigated the physiological properties of IL-34 on TECs damage caused by cisplatin-nephrotoxicity (CP-N).

Method
7-week-old male C57BL/6 (B6) mice (n=16) were fasted for 8 hours and then induced CP-N by intraperitoneal injection (IP) of CP (25 mg/kg) on day 0. Groups of animals were given either anti-mouse IL-34 antibody (CP+anti-IL-34 Ab, 400 ng/kg, n=8) or vehicle (CP+V, equal volume of saline, n=8) daily by IP from day -1 to day 2. Three age-matched male B6 mice were used as normal control (NC). All mice were sacrificed on day 3. In addition, mouse renal proximal TECs (MRTEpiC) were cultured to analyze the inhibitory effects of IL-34 on CP-induced TEC apoptosis. Cells were stimulated with CP (2 μg/mL), then treated with or without anti-IL-34 Ab (1000 pg/mL).

Results
Compared to the NC, CP+V mice exhibited marked acute kidney injury (AKI) and upregulated expression of IL-34 and its two receptors, cFMS and PTP-ζ. Compared to the vehicle treatment, anti-IL-34 Ab treatment significantly suppressed the intrarenal expression levels of IL-34 and its two receptors in CP-N mice; it also significantly suppressed serum IL-34 levels (72.1 ± 5.6 vs. 40.4 ± 7.5 pg/mL, p=0.013). Additionally, treatment with anti-IL-34 Ab significantly improved serum Cr levels (1.3 ± 0.2 vs. 0.7 ± 0.1 mg/mL, p=0.033), ameliorated tubulointerstitial injury (numbers of casts/HPF: 11.9 ± 2.6 vs. 6.5 ± 1.8, p=0.048), and suppressed the number of F4/80+ Mø (17.5 ± 2.7 vs. 11.1 ± 1.1/HPF, p=0.041) and TUNEL+ apoptotic cells (29.2 ± 4.9 vs. 16.7 ± 2.7/HPF, p=0.036) in CP-N mice. The renal cortical transcript levels of Kim-1, MIP-1/CCL3, TNF-α, and Bax were significantly lower in the CP+anti-IL-34 Ab mice than in the CP+V mice. Furthermore, the CP+anti-IL-34 Ab mice showed significantly less renal infiltration of CD11b+F4/80+TNF-α+ cells. In vitro, stimulation with CP induced the expression of IL-34 and its two receptors in MRTEpiC. Treatment with anti-IL-34 Ab significantly suppressed CP-induced caspase-3 and Bax expression with degradation of ERK1/2 phosphorylation in the damaged MRTEpiC.

Conclusion
IL-34 secreted from damaged TECs was involved in the progression of CP-N. Inhibition of IL-34 with neutralizing antibody directly prevented CP-induced TEC apoptosis by inhibiting the phosphorylation of ERK1/2. Blocking of IL-34 might suppressed proliferation of cytotoxic Mø, which indirectly led to the attenuation of CP-N. Thus, IL-34 represents a potential as therapeutic target for AKI with TECs injury.
P0532CD8+CD103+ INDUCED REGULATORY T CELLS BUT NOT NATURE REGULATORY T CELLS AMELIORATE IR-INDUCED KIDNEY INJURY
Authors: Xu Tongtong , Xu Zhenjian , Chen Liling , Xu Anping 
Published: June 2020

Abstract

Background and Aims
Acute kidney injury (AKI) is one of the most common complications in clinical practice, but current approaches offer no cures for AKI. Inflammatory response is the key mechanism of ischemia reperfusion (IR)-induce AKI, known as hypoxia/reoxygenation injury. T lmphocytes are crucial mediators of IR-induced AKI. It is reported that regulatory T cell (Treg) has potential ability to ameliorate IR-induced AKI. Tregs consist of nature Treg (nTreg) and induced Treg (iTreg), which are well established to blunt immune responses. We confirmed that CD8+CD103+iTreg remain steadily and barely transfer into Th17, which produce proinflammatory response, under inflammatory response. It is studied that nTreg tends to transfer into Th17 under inflammatory condition, which clarifies the instability of nTreg. Thus, the instability of nTreg under inflammatory response hints us that nTreg are not suitable for recovery from IR-induced AKI. Accordingly, we studied the role of CD8+CD103+iTreg in repair after IR-induced kidney.

Method
In vitro study, we test the expression of CD103, Foxp3 and IL-17a in CD8+CD103+iTreg under 1% O2 concentration. In vivo study, SPF C57BL/6J male mice (8-10 weeks old, body weight 20-25g) were divided into four groups, sham-operated control group, AKI group, iTreg treatment group and nTreg treatment group, with 6 mice in each group. On the day of surgery, we anesthetize the mice (pen-tobarbital sodium, 50 mg/kg body weight). Mice in the AKI group were reperfused after 25 minutes of bilateral renal artery ischemia. We injected CD8+CD103+iTreg (2 × 106/mouse) or nTreg (2 × 106/mouse) intraperitoneally after 24 hours of modeling to the treatment group and euthanized the mice on the third day of anesthesia.

Results
We discovered that the expression of CD103 is stable in CD8+iTreg in vitro under 1% O2 concentration (Figure 1, 2). In addition, their inhibiting abilities of T cells proliferation in vitro remain steadily (Figure not shown). However, CD8+CD103+iTreg seldom transfer into Th17, but remain Foxp3 under hypoxic condition (Figure 2). Adoptively transferring CD8+CD103+iTregs, a new subpopulation of CD8+iTreg we have identified, to AKI mice, we found that these cells can ameliorate the development of AKI by mitigating the level of serum creatine, alleviating acute tubular necrosis (ATN) and decreasing the mortality of AKI.

Conclusion
Therefore, we confirmed that CD8+CD103+iTreg is stable under inflammatory(hypoxic) environment. Thus, CD8+CD103+iTreg targeting may be a novel therapeutic approach to enhance recovery from IR-induced AKI.
P0537LINARIN PROTECTS KIDNEY AGAINST ISCHEMIA/REPERFUSION INJURY VIA INHIBITION OF ETS2
Authors: Yang Chengyu , Xu Yan 
Published: June 2020

Abstract

Background and Aims
Ischemia/reperfusion injury (IRI), a participant in acute kidney injury (AKI), can occur as a series of pathological processes such as inflammation. Linarin (LIN) has been widely used for different diseases. To confirm the anti-inflammatory value and relevant mechanism of LIN during IRI, in vivo and vitro model were established.

Method
LIN or isovolumetric DMSO was given, and histologic analysis, quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR), serum creatinine (SCr) testing and blood urea nitrogen (BUN) were used to evaluate kidney injury. Microarray analysis, protein-protein interaction (PPI) analysis and molecular docking were used to identify target protein of LIN.

Results
At first, we find that LIN could inhabit the kidney injury in vivo IRI model and decrease the expression of IL-12 p40 in vitro IRI model. To explore the mechanism of LIN, we collected raw data from public microarray database and identified E26 oncogene homolog 2 (ETS2) as a target protein of LIN according to microarray analysis, PPI and molecular docking. The contact area is highly conserved and located on a protein-protein interaction domain of ETS2 which indicated that LIN may alter the interaction with synergistical protein in the regulation of IL-12 p40 expression.

Conclusion
Our study demonstrated the anti-inflammatory effect of LIN during IRI-triggered AKI, broadening the medicinal value of LIN and the therapeutic options for IRI-triggered AKI.
P0540EFFECT OF MEMBRANE MATERIALS ON VANCOMYCIN, TEICOPLANIN AND LINEZOLID REMOVAL DURING CONTINUOUS RENAL REPLACEMENT THERAPIES: AN IN VITRO STUDY
Authors: Godi Llaria , Lorenzin Anna , De Cal Massimo , Ronco Claudio 
Published: June 2020

Abstract

Background and Aims
In a continuous renal replacement therapy (CRRT) scenario, removal of anti-methicillin resistant Staphylococcus Aureus agents can be quantitatively important, thereby contributing to clinically relevant decreases in their plasma concentration during treatment. Extracorporeal elimination of antimicrobial agents is influenced by the dose and modality prescribed, as well as the sieving coefficient (SC) and adsorptive properties of the membrane used.The aim of this study was to document the specific SC and adsorptive capacity of three different membrane materials related to vancomycin, teicoplanin and linezolid.

Method
This in vitro study used a model of continuous veno-venous hemofiltration. 500 ml of whole blood from healthy donor spiked with one antibiotic under investigation was pumped (blood flow of 50 ml/min and ultrafiltrate flow of 10 ml/min) in a closed-circuit using polysulfone (PS), polymethylmethacrylate (PMMA) and polyacrylonitrile (PAN) membranes. Samples were collected from in-flow, out-flow and ultrafiltrate lines in a 360 min period. Antibiotic concentrations were measured to calculate SCs. Mass balance analysis was assessed to evaluate the adsorptive capacity of PS, PMMA and PAN membrane related to each antibiotic.

Results
The SCs were substantially affected by the hemodialyzers material in the case of Vancomycin, where PMMA membrane had higher SC (SC=0.89±0.01) compared to PAN (SC=0.79±0.02) and PS (SC=0.62±0.03) membranes. The effect of material was minor for Teicoplanin (Sc=0.12±0.05 for PS, Sc=0.17±0.05 for PMMA, Sc=0.19±0.00 for PAN) and no noticeable difference within hemodialyzers was found for Linezolid (Sc=0.92±0.03 for PS, Sc=0.95±0.01 for PMMA, Sc=0.95±0.00 for PAN). In terms of adsorptive capacity, PS and PMMA membranes showed higher interaction with Vancomycin and Teicoplanin compared with PAN membrane, while a small amount of Linezolid was adsorbed by all the three filters. The cumulative adsorbed amount of PS and PMMA of Teicoplanin were also clinically relevant (99.15 mg/m2 and 51.33 mg/m2 respectively) compared to PAN membrane (9.14 mg/m2).

Conclusion
PS, PMMA and PAN membranes behave differently in terms of sieving and adsorptive properties related to vancomycin, teicoplanin and linezolid. These differences may have a clinical influence on vancomycin and teicoplanin removal during CRRT, while linezolid variability during CRRT hasn’t to be ascribed for membrane material.
P0555HYPOTHERMIA ATTENUATES CHRONIC RENAL INJURY AFTER ISCHEMIA-REPERFUSION IN KIDNEY
Authors: Na Ki Ryang , CHOI DAE EUN , Lee Kang Wook , Kim Dabi , Kim Eunji , Jeong Jin Young , Ham Young Rok , Kim Haeri , Choi Wonjung , Chang Yoon-Kyung 
Published: June 2020

Abstract
Background and Aims: Hypothermia attenuates the renal injury induced by ischemia-reperfusion(IR). However, the detailed molecular pathway remains unknown. Although there has been reported that hypothermia protects acute renal damage, there is little known that hypothermia reduce renal fibrosis in IR kidney injury. We evaluated hypothermic protection against renal fibrosis in renal IR injury. Method: C57Bl/6 mice were divided into the following groups: sham-operated (cold, 32C) vs normal temperature (37C); IR mice (32C vs 37C). Kidneys were harvested 10 and 27 minutes after induction of renal ischemia and 24, 72, 168 hours after iIR injury. Functional and molecular markers of kidney injury were evaluated. Results: The blood urea nitrogen and serum creatinine levels and the histologic renal injury scores were significantly lower in 32C IR than 37C IR kidneys (all P values &lt; .05).In kidney harvested 10 and 27 min, the extent of renal AMPK,ERK, and HIF1 phosphorylation was significantly increased in the kidneys of 32C compared to 37C IR mice. In kidney harvested 27 min, 24hr, 72hr, and 168hr, the expression levels of SOX9, TGF beta, alpha SMA, collagen IV, and fibrinogen decreased in 32C IR compared to 37C IR mice. In addition, in kidney harvested 72hr, and 168hr, the stained area of TGF beta, alpha SMA, and masson trichrome, were significantly decreased in 32C IR compared to 37C IR mice. Conclusion: Hypothermia attenuates the renal fibrosis induced by Ischemia reperfusion.
P0557HYPERBARIC OXYGEN PRECONDITIONING INCREASES HEME OXYGENASE 1 EXPRESSION IN KIDNEY TISSUE AND IMPROVES KIDNEY FUNCTION IN SPONTANEOUSLY HYPERTENSIVE RATS WITH ISCHEMIC ACUTE KIDNEY INJURY
Authors: Ivanov Milan , Miloradovic Zoran , Mihailovic-Stanojevic Nevena , Jovovic Djurdjica , Karanovic Danijela , Vajic Una-Jovana , Jeremić Rada , Djelic Marina , Brkic Predrag 
Published: June 2020

Abstract

Background and Aims
Renal ischemia–reperfusion (RIR) injury is one of the factors in the development of acute kidney injury (AKI). AKI is multifactorially caused, but the mechanism of pathogenesis and development of this disease is still incompletely defined. AKI is characterized by the sudden appearance, rapid progression of disease and very uncertain and often fatal outcome. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that catalyzes the breakdown of heme to biliverdin, carbon monoxide, and iron. HO-1 is now recognized as a protection factor in acute kidney injury. The aim of this study was to determine the effect of preconditioning with hyperbaric oxygen (HBO) on HO-1 expression in kidney tissue and kidney function in spontaneously hypertensive rats (SHR) during kidney ischemia–reperfusion injury.

Method
An experiment was performed in anesthetized, adult six-month-old male SHR. The right kidney was removed and the renal ischemia was performed by clamping the left renal artery for 40 minutes. SHR were randomly selected in three experimental groups: sham operated group (SHAM; n=7); AKI control group (AKI; n=9); and AKI group with HBO (AKI+HBO; n=9). Treated group were placed into experimental HBO chambers and exposed to pure oxygen, twice a day (in a 12 hour period, 8AM and 8 PM) for two consecutive days in the following manner: 10 minutes slow compression, 2.026 bar for 60 minutes, 10 minutes slow decompression. Mean arterial pressure (MAP) and HO-1 expression in kidney tissue were measured 24h after reperfusion. Clearance of creatinine (CCr), urea (CUr) and phosphate (CPh) were calculated 24h after reperfusion.

Results
After AKI induction reduction of blood pressure was recorded in both groups with AKI. Preconditioning with HBO significantly improved kidney function in rats with AKI compared to control group. HO-1 expression in kidney tissue was significantly higher in the treated group (p&lt;0,01) compared to SHAM and AKI control group.

Conclusion
Our results suggest that HBO treatment improves kidney function in the AKI+HBO vs. AKI control group. This implies that increased level of HO-1 due to preconditioning with hyperbaric oxygen may have beneficial effects on kidney function, and potentially protective effect in an ischemic model of AKI with hypertension.