bluuebunny/crossref_metadata_2025_split huggingface dataset:
P0011THE ROLE OF AQUAPORIN-11 (AQP11) IN THE THYMUS DEVELOPMENT
Authors: Masaka Kei , Tanaka Yasuko , Ishibashi Kenichi 
Published: June 2020

Abstract

Background and Aims
Some aquaporins transport not only water but also small non-ionic molecules such as glycerol. In fact, aquaporin-9 (AQP9) has been shown to transport glycerol which is critical to support memory T cell survival through metabolic fitness (Cui G et al. Cell. 161:750, 2015). As AQP11 is widely expressed and transport glycerol as well as water, AQP11 may also play a role in immunological system, which will expand the repertoire of the aquaporin research field.

Method
The AQP11 expression in the thymus was examined by RT-PCR, Western blot and immunohistochemistry in mice. Phenotypic analysis and microarray analysis of the thymus were conducted in wild and AQP11 null mice at 21 day old before the development of uremia due to polycystic kidneys.

Results
Both mRNA and protein expressions of AQP11 in the thymus were higher than those of the kidney by RT-PCR and Western blot. Interestingly, the size of the thymus from AQP11 null mice was smaller than that of the wild mice: 28mg vs. 56mg, even after the correction by the body weight: 0.59 % vs. 0.82 %, as the body size of AQP11 null mice was smaller. The vacuolated medullary epithelial cells were observed in the thymus of AQP11 null mice with narrowed cortex. The immunohistochemical analysis revealed the AQP11 expression at the stromal-epithelial cells in the thymus. The microarray analysis of the gene expression in the thymus was compared between the wild and AQP11 null thymus by the annotation analysis based on the David Bioinformatics Resources 6.8 (beta). The up-regulated 66 genes more than 1.5 folds in AQP11 null thymus are mainly related to the PI3K/Akt signaling pathway to promote metabolism, proliferation, cell survival, growth and angiogenesis. On the other hand, the down-regulated 55 genes less than half in AQP11 null thymus are related to energy production and the peroxisome proliferator-activated receptor (PPAR) signaling pathway. Further RT-qPCR analysis confirmed the enhanced expression of Egfr (Epidermal Growth Factor Receptor), Itgb4 (Integrin beta-4) and Il2ra (interleukin 2 receptor alpha) and the diminished expression of aquaglyceroporin AQP7, Pck1 (Phosphoenolpyruvate carboxy-kinase 1) and Ucp1 (Mitochondrial uncoupling protein 1). The up-regulated genes for growth signaling was unexpected with the smaller thymus but may support the survival of the hypoplastic thymus as a compensation. On the other hand, the down-regulated genes may compromise fat-glucose-energy metabolism in the thymus leading to the smaller thymus, which may be aggravated by the decreased expression of AQP7, another glycerol channel.

Conclusion
AQP11 may play an important role in the metabolic control of the developing thymus possibly through its glycerol transport. The smaller thymus with narrower cortex in AQP11 null mice may lead to immunological dysfunction, which is currently under study.
P0014MYELOID-SPECIFIC TARGETING OF NOTCH AMELIORATES RENAL FIBOSIS VIA REDUCED INFILTRATION AND ACTIVATION OF BONE MARROW-DERIVED MACROPHAGE
Authors: Jiang Yali 
Published: June 2020

Abstract

Background and Aims
Macrophages play critical roles in renal fibrosis. However, macrophages exhibit ontogenic and functional heterogeneities, and which population of macrophages contributes to renal fibrosis and the underlying mechanisms remain unclear.

Method
In this study, we genetically targeted Notch signaling by disrupting the transcription factor recombination signal binding protein-Jκ (RBP-J), to reveal its role in regulation of macrophages during the unilateral ureteral obstruction (UUO)-induced murine renal fibrosis.

Results
Myeloid-specific disruption of RBP-J attenuated renal fibrosis with reduced extracellular matrix deposition and myofibroblast activation, as well as attenuated epithelial-mesenchymal transition, likely owing to the reduced expression of TGF-β. Meanwhile, RBP-J deletion significantly hampered macrophage infiltration and activation in fibrotic kidney, although their proliferation appeared unaltered. By using macrophage clearance experiment, we found that kidney resident macrophages made negligible contribution, but bone marrow (BM)-derived macrophages played a major role in renal fibrogenesis. Further mechanistic analyses showed that Notch blockade reduced monocyte emigration from BM by down-regulating CCR2 expression. Finally, we found that myeloid-specific Notch activation aggravated renal fibrosis, which was mediated by CCR2+ macrophages infiltration.

Conclusion
In summary, our data have unveiled that myeloid-specific targeting of Notch could ameliorate renal fibrosis by regulating BM-derived macrophages recruitment and activation, providing a novel strategy for intervention of this disease.
P0015SIRT2 REGULATES CISPLATIN-INDUCED ENDOPLASMIC RETICULUM STRESS THROUGH HEAT SHOCK FACTOR 1 DEACETYLATION
Authors: Park Woong , Kim Hyeongwan , Jung Yujin , Kang Kyung Pyo , Kim Won 
Published: June 2020

Abstract

Background and Aims
Nephrotoxicity is an important cisplatin-induced adverse reaction and restricts the use of cisplatin to treat malignant tumors. Endoplasmic reticulum (ER) stress is caused by the accumulation of misfolded proteins, and is induced by cisplatin in kidneys. SIRT2 nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase is a member of the sirtuin family, but its role in cisplatin-induced ER stress remains unclear.

Method
To investigate the effect of SIRT2 on cisplatin-induced ER stress using SIRT2 knockout mice and human proximal tubular epithelial cells (HK-2 cells). We treated cisplatin (20 µg/mL) or induced by intraperitoneal injection of cisplatin (20 mg/kg) and evaluated the changes of ER stress and its signal mechanism.

Results
Cisplatin administration was found to significantly increase the expressions of PRKR-like ER kinase (PERK), phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), and the C/EBP homologous protein (CHOP) and caspase-12 in the kidneys of SIRT2-wild type mice. However, cisplatin-induced increases in the expressions of p-PERK, p-eIF2α, CHOP and, caspase-12 were diminished in kidneys of SIRT2 knockout mice. In vitro, cisplatin significantly increased the expressions of p-PERK, p-eIF2α, CHOP, and caspase-12 in HK-2 cells. When the effect of SIRT2 on cisplatin-induced ER stress was evaluated using SIRT2-siRNA (ON-TARGET plus human SIRT2 siRNA) or the SIRT2 inhibitors, AGK2 and AK1, knockdown or inhibition of SIRT2 significantly attenuated the cisplatin-induced protein expression of p-PERK, p-eIF2α, CHOP, and caspase-12. Immunoprecipitation studies showed SIRT2 bound physically to heat shock factor (HSF)1 and that HSF1 acetylation was significantly increased by cisplatin. In addition, knockdown of SIRT2 increased cisplatin-induced HSF1 acetylation and increased the expression of heat shock protein (HSP)70.

Conclusion
These observations suggest that suppression of SIRT2 ameliorates cisplatin-induced ER stress by increasing HSF1 acetylation and HSP expression.
P0018GLOMERULAR ENDOTHELIAL CELL SENESCENCE DRIVES AGE-RELATED KIDNEY DISEASE THROUGH PAI-1
Authors: Cohen Camille , Oceanc Legoff , Soysouvanh Frederic , Tanou Marine , Vasseur Florence , Nguyen Clement , Amrouche Lucile , Meunier Tanguy , Rabant Marion , Nochy Dominique , Legendre Christophe , Anglicheau Dany , Milliat Fabien , Terzi Fabiola 
Published: June 2020

Abstract

Background and Aims
In age-related chronic kidney disease (CKD), the most frequent histological lesion observed is glomerulosclerosis. The molecular mechanisms involved in this deterioration process are unclear, but cellular senescence might play a role.

Method
By combining several murine models of physiological and accelerated aging with transgenic animals and in vitro models, we discovered the role of endothelial senescence in the development of glomerular lesions.

Results
These senescent glomerular endothelial cells secreted several molecules, grouped under the senescence associated secretory phenotype (SASP) including the plasminogen activator inhibitor 1 (PAI-1). Specific deletion of PAI-1 in endothelial cells prevented the development of glomerulosclerosis during physiological and accelerated aging, by decreasing podocyte loss. In addition, we showed that PAI-1 mediates a detrimental endothelial-podocyte crosstalk, as incubation of podocytes by supernatant of senescent glomerular endothelial cells led to their detachment. Consistently, preincubation of the senescent supernatant with tiplaxtinin, a PAI-1 inhibitor, preserved podocytes. More importantly, we demonstrated that these data are relevant to humans. In fact, PAI-1 staining the day of the transplantation was predictive of kidney allograft dysfunction 12 months after transplantation from elderly donors.

Conclusion
In conclusion, our study uncovers the critical role played by endothelial senescence in the development of glomerulosclerosis during aging and identified PAI-1 as a novel promising biomarker for predicting kidney dysfunction in patients receiving a kidney from elderly donors.
P0024TRIPARTITE MOTIF-CONTAINING 55 (TRIM55) PARTICIPATES IN THE IMMUNE RESPONSE IN THE EXPERIMENTAL ANTI-THY1 GLOMERULONEPHRITIS
Authors: Chen Lei , Jiang Hongli 
Published: June 2020

Abstract

Background and Aims
Mesangial proliferative glomerulonephritis (MsPGN) is considered as an immune- related disease. In the previous study, tripartite motif family was reported to be closely related to immune regulation. Therefore, we performed a series of experiments in vivo and vitro to investigate the role of tripartite motif-containing 55 (TRIM55), a member of tripartite motif family, in the progression of MsPGN.

Method
36 male SD rats were randomly divided into 6 groups to induce anti-Thy1 nephritis. Specimens of the negative control group were collected at 0d after the injection, while those of other groups were collected at 1d, 2d, 3d, 4d, 5d after the injection, respectively. Renal cortex slices were obtained for histological and immunohistochemistry assessmen of CD68. qPCR analysis of glomerulus was performed to examine the expression of TRIM55 . Primary RMCs with overexpression of TRIM55 were obtained through plasmid transfection. In addition, si-RNA tranfection was used to knock down the expression of TRIM55 in primary RMCs. qPCR analysis was conducted to detect the level of cytokines, such as TNF-α, CCL2, CXCL6, CXCL10, and IL-6.

Results
PAS staining results indicated mesangial dissolution occurred since 1d, followed by inflammatory cell infiltration. CD68 immunohistochemical staining results showed that macrophages infiltration peaked at 1d and then decreased gradually. The expression of TRIM55 mRNA also peaked at 1d and decreased gradually, which was consistent with the trend of macrophages infiltration. In primary RMCs, knockdown of TRIM55 led to down-regulation of the expression of cytokines (TNF-α, CCL2, CXCL6, CXCL10 and IL-6). On the other hand, the expression of those cytokines(TNF-α, CCL2, CXCL6, CXCL10 and IL-6) significantly increased in TRIM55-overexpressed primary RMCs.

Conclusion
The above results indicate that TRIM55 participates in the immune response in experimental anti-Thy1 glomerulonephritis by regulating the production of cytokines. We duce TRIM55 may be a promising therapeutic intervention to ameliorate leukocyte infiltration in MsPGN.
P0025BARIATRIC SURGERY MAY REDUCE UPREGULATED EXPRESSION OF FIBROBLAST GROWTH FACTOR 21 AND ANGIOTENSIN-CONVERTING ENZYME 2 IN OBESE PATIENTS
Authors: Yu Byung Chul , Kim Hyoungnae , Park Mooyong , Kwon Soon hyo 
Published: June 2020

Abstract

Background and Aims
Recent studies showed that the fibroblast growth factor 21 (FGF21) and angiotensin-converting enzyme 2 (ACE2)/Angiotensin 1-7 (Ang (1-7))/MAS axis of the renin-angiotensin system counteract to the negative role of Ang II in various disease. In this study, we examed FGF21 and ACE2/Ang (1-7) in obesity and its change after bariatric surgery.

Method
We prospectively enrolled obese patient who performed bariatric surgery and age-sex matched healthy volunteers (HV) (n=12 each). We obtained their clinical information and serum samples. Serum FGF-21, Ang II, ACE2, and Ang (1-7) levels were measured by enzyme-linked immunosorbent assay kits. We measured also FGF-21, Ang II, ACE2, and Ang (1-7) 6 months after bariatric surgery in obese patients (n=12).

Results
FGF21, Ang II, and ACE2 levels were significantly higher in obese patients compared with HV (p= 0.045, &lt; 0.001, and 0.020, respectively). FGF21, Ang II, and ACE2 levels were significantly decreased after bariatric surgery (p = 0.002, 0.005, and 0.023, respectively). There was no significant difference in Ang (1-7) levels between obese patients and HV (p = 0.887) (Figure 1). Although Ang (1-7) levels did not change after bariatric surgery (p = 0.480), changes in Ang (1-7) levels were positively correlated with changes in body mass index (BMI) (R2 = 0.580, p = 0.048) (Figure 2).

Conclusion
FGF21 and ACE2 were upregulated in obese patients and they are reduced after bariatric surgery. A decrease in BMI after bariatric surgery could lead to decrease in Ang (1-7).
P0031IS OXIDATIVE STRESS ASSOCIATED WITH TOTAL KIDNEY VOLUME IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE?
Authors: Dogan Ibrahim , Eser Baris , Aydemir Nihal , Kayadibi Huseyin , Ozcan Oguzhan , Fidan Nurdan , Ozkurt Sultan 
Published: June 2020

Abstract

Background and Aims
Ischemia Modified Albumin (IMA) is a marker of cardiovascular risk factor associated with oxidative stress. In this study, our aim was to determine oxidative stress status in autosomal dominant polycystic kidney disease (ADPKD) and to evaluate its relationship with total renal volume.

Method
Seventy-two ADPKD (mean age 52 (41-64) years) and 33 healthy controls (mean age 54 (42-62) years) (P= 0.372) were included in the study. Total Oxidant Level (TOS) and Total Antioxidant Level (TAS) were measured using the colorimetric method. Oxidative Stress Index (OSI) was calculated. IMA level was measured by ELISA. Total renal volume was assessed by magnetic resonance imaging. The relationship between oxidative stress, inflammation and renal volume was evaluated by correlation analysis. P values &lt;0.05 were considered significant for statistical analyses.

Results
Serum IMA level was higher in the patient group (158.46 ng/ml (85.98-246.70)) than in the control group (70.04 ng/ml (50.40-80.02); (P&lt; 0.001). TOS level and OSI rate were significantly higher in the patient group compared to the control group, and TAS level was not different between the two groups (P&lt; 0.001, P&lt; 0.001, P= 0.576, respectively).Correlation analysis was performed between IMA, TAS and TOS levels, OSI rate and kidney volume. IMA level correlated with TOS level and OSI positively (P&lt; 0.001), but there was no correlation between IMA level and TAS level and renal volume (P= 0.550, P= 0.286, respectively). IMA level was negatively correlated with GFR and positively correlated with proteinuria (P= 0.040, P&lt; 0.001, respectively). There was no correlation between total renal volume and IMA, TAS, CRP and proteinuria. The correlation between volume and GFR and TOS level was borderline negative (P= 0.054, P= 0.051, respectively).

Conclusion
There is an increased level of oxidative stress in ADPKD. Increased IMA level may show oxidative stress in this population. Total renal volume in ADPKD is associated with loss of renal function but not sufficient to show oxidative stress.
P0038WATER RESTRICTION INDUCES THE SHORTENING OF PRIMARY CILIA IN KIDNEY TUBULAR CELLS
Authors: Park Kwon Moo , Kong Min Jung 
Published: June 2020

Abstract

Background and Aims
The primary cilia play a key role in the maintenance of cell homeostasis by sensing and transducing extracellular signals into the cell and are associated with several kidney diseases including ADPKD. Here, we investigated whether water restriction affects the length of primary cilia of kidney tubule cells and its underlying mechanisms.

Method
Some mice were not supplied with water for 2 days and then the length of primary cilia were determined by immunostaining using acetylated-α-tubulin (ac-α-tubulin) antibody. Madin-Darby canine kidney (MDCK) cells were exposed to high concentration of NaCl or mannitol and the lengths of primary cilia were determined under microscope.

Results
Water restriction shortened primary cilia length in kidney tubular cells along with the increase of urine osmolality. Water restriction lowered the expression of acetylated-α-tubulin (ac-α-tubulin), EXOC5, one of the components of exocyst complex, and α-tubulin transferase in the kidney. In MDCK cells, high concentration of NaCl or mannitol treatments shortened primary cilia length and decreased the expression of ac-α-tubulin, EXOC5, and α-tubulin transferase.

Conclusion
These findings demonstrate that water restriction induces the shortening of primary ciliua in kidney tubule cells along with increased urine osmolality, suggesting that primary cilia are involved in the urine concentric process.
P0039IS A NEPHRECTOMY POLYCYSTIC KIDNEY DISEASE NECESSARY FOR PATIENTS WITH END-STAGE CHRONIC KIDNEY DISEASE?
Authors: Perlin Dmitriy , Dymkov Ivan 
Published: June 2020

Abstract

Background and Aims
In the structure of end-stage CKD polycystic kidney disease is about 8-10 %. These patients often required preparation for transplantation. In addition, enlarged kidneys are reducing the volume of the abdominal cavity, negative impact on the peritoneal dialysis (PD).

Method
In 2005-2019 41 nephrectomies were performed in patients with end-stage CKD with polycystic kidney disease: 11 patients have undergone open nephrectomy, 13 patients laparoscopic nephrectomy and 17 retroperitoneoscopic nephrectomy. We analyzed postoperative period and complications, method of treatment end-stage CKD selected in future. In particular, we evaluated the effectiveness of peritoneal dialysis depending on the operating access.

Results
Complications: intraoperative bleeding was in 3 cases, damage of the spleen was in one. The significantly lower blood loss was in the group of operations performed endoscopic access. Subsequently, 16 patients were treated with hemodialysis (HD), 25 patients PD. The effectiveness of PD was estimated by 3 months and 1 year after start treatment by kt/v. In the group of patients with open nephrectomy, the effectiveness on average was 1.61 and 1.44 respectively. Patients underwent laparoscopic nephrectomy the efficiency is in average of 1.72, and 1.60, retroperitoneoscopic nephrectomy 1.88, 1.72 respectively. The conversion method of PD-treatment to the HD within 6 months after surgery was required in 5 patients (open nephrectomy technique), 2 patients (laparoscopic technique), no one patient (retroperitoneoscopic technique) was not required for the conversion PD to HD.

Conclusion
Our experience of nephrectomies in patient with end-stage CKD indicate the safety and effectivity of the endoscopic technique and its applicability to patients on PD. Retroperitoneoscopic access has less impact on the effective area of the peritoneum, which is reflected in the subsequent course of PD.
P0077A NEW MUTATION OF DNAJB11 AS A CAUSE OF CYSTIC KYDNEY DISEASE: THE FOURTH GENE OF ADPKD
Authors: Pisani Isabella , Allinovi Marco , Palazzo Viviana , Gentile Micaela , Giglio Sabrina , Fiaccadori Enrico , Manenti Lucio 
Published: June 2020

Abstract

Background and Aims
Monogenic inherited diseases are an underestimated but important cause of chronic kidney disease (CKD). Despite the increasing knowledge about their inheritance, they are identified in fewer than 10% of CKD patients. Among monogenic causes of CKD, polycystic kidney diseases (PKD) represent a group of disorders with a clinical and genetic heterogeneity and a variable phenotype (from early manifestations during pregnancy or childhood to the absence of clinical manifestations until adulthood). We here present a PKD family with 5 members displaying the disease (Figure 1).

Method
We revised patients clinical history, laboratory data and imaging exams. An accurate family history was recovered. Blood samples were collected from living patients to perform an exome analysis using next generation sequencing to analyze all possible genes involved in PKD.

Results
Each patient presented a clinical history of nephrolithiasis, a variable degree of CKD (from normal kidney function to renal transplant), urinary and blood parameters compatible with distal renal tubular acidosis (hypercalciuria, low urinary citrate excretion and hypokalemia). Imaging exams showed several renal cysts in the medulla or at the cortico-medullary junction with intracystic calcifications (Figure 2). Some patients displayed also large cortical renal cysts and also hepatic and pancreatic cysts. The genetic analysis performed using next generation sequencing in four patients showed a new mutation on the gene DNAJB11; the mutation introduced a stop codon and was identified as pathogenic by prediction programs. It was present in heterozygosity in all subjects and had an autosomal dominant pattern of inheritance.

Conclusion
DNAJB11 mutations were reported as a cause of PKD for the first time in 2018 by Cornec-Le-Gall and colleagues. The nephropathy derived from these mutations need to be differentiated from ADPKD (autosomal dominant polycystic kidney disease), from ADTKD (autosomal dominant tubulointerstitial kidney disease) and from medullary sponge kidney. DNAJB11 encodes a co-chaperone of the endoplasmic reticulum (ER) also called ERdj3. It is part of the HSP40 protein family and plays a central role in both intracellular and extracellular proteomic homeostasis (proteostasis). In the intracellular compartment it acts as a co-chaperone in the pathway of the unfolded protein response (UPR) in which it binds misfolded proteins which have to be secreted and activates BiP an HSP70 of ER whose function is to correct the misfolding. In the kidney it is mainly expressed in the thick ascending limb of Henle’s loop, in the distal tubule and in the collecting duct justifying the clinical presentation of nephropathy and differentiating the disease from ADPKD (Figure 3).