Endothelin and Podocyte Injury in Chronic Kidney Disease

2011 ◽  
pp. 120-138 ◽  
Author(s):  
Cécile Fligny ◽  
Matthias Barton ◽  
Pierre-Louis Tharaux
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Podocyte Injury

Implementation of a human podocyte injury model of chronic kidney disease for profiling of renoprotective compounds

2017 ◽  
Vol 815 ◽  
pp. 219-232 ◽  
Author(s):  
Vivek C. Abraham ◽  
Loan N. Miller ◽  
Steve D. Pratt ◽  
Brent Putman ◽  
Laura Kim ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Podocyte Injury ◽  
Injury Model

scholarly journals Weighted Gene Correlation Network Analysis (WGCNA) Detected Loss of MAGI2 Promotes Chronic Kidney Disease (CKD) by Podocyte Damage

2018 ◽  
Vol 51 (1) ◽  
pp. 244-261 ◽  
Author(s):  
Zhi Zuo ◽  
Jian-Xiao Shen ◽  
Yan Pan ◽  
Juan Pu ◽  
Yong-Gang Li ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Network Analysis ◽  
Kidney Disease ◽  
Kidney Diseases ◽  
Correlation Network ◽  
Hub Genes ◽  
Podocyte Injury ◽  
Protein Levels ◽  
Podocyte Damage ◽  
Gene Correlation

Background/Aims: Podocyte damage is associated with proteinuria, glomerulosclerosis and decline of renal function. This study aimed to screen critical genes associated with podocyte injury in chronic kidney disease (CKD) by weighted gene correlation network analysis (WGCNA), and explore related functions. Methods: GSE66107, GSE93798, GSE30528, GSE32591 gene expression data including podocyte injury models or glomeruli in CKD patients were downloaded from the GEO database. R was used for data analysis. Differentially expressed genes (DEGs) (FDR< 0.05 or |Fold Change|≥1.5) in GSE993395 were assessed by WGCNA. According to Gene Ontology (GO) and known podocyte standard genes (PSGs), podocyte injury-associated modules were defined, with hub genes selected based on average intramodular connectivity. The Cytoscape software was used for network visualization. Nephroseq was used to assess the clinical significance of hub genes. Small interfering RNA (siRNA) was used to evaluate the roles of hub genes in podocyte injury Results: Totally 7957 DEGs were screened, with 15 (co.DEGs) altered in all 4 datasets; 4031 DEGs were used for WGCNA, encompassing 12 modules. Green modules (most PSGs and co.DEGs) were significantly enriched in glomerular development, and considered podocyte injury-associated modules. Furthermore, MAGI2 (a hub gene) was also a co.DEG and PSG. Glomerular MAGI2 levels were reduced in various kidney diseases, and positively and negatively associated with glomerular filtration rate and urinary protein levels in CKD patients. Moreover, MAIG2 knockdown reduced NPHS2, CD2AP and SYNPO levels, and induced podocyte rearrangement and apoptosis. Conclusion: MAGI2 identified by WGCNA regulates cytoskeletal rearrangement in podocytes, with its loss predisposing to proteinuria and CKD.

scholarly journals Clinical and laboratory characteristics of the patterns of chronic kidney disease in patients with type 2 diabetes

2020 ◽  
Vol 22 (6) ◽  
pp. 515-525
Author(s):  
Vadim V. Klimontov ◽  
Anton I. Korbut ◽  
Olga N. Fazullina ◽  
Ilya V. Vinogradov ◽  
Vyacheslav V. Romanov
Keyword(s):  
Risk Factors ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Urinary Excretion ◽  
Cross Sectional Study ◽  
Channel Blockers ◽  
Cross Sectional ◽  
Podocyte Injury

BACKGROUND: A growing body of evidence demonstrates increasing prevalence of normoalbuminuric chronic kidney disease (NA-CKD) in subjects with type 2 diabetes (T2D), while proportion of albuminuric pattern is decreasing. AIMS: To determine the clinical and laboratory parameters associated with different patterns of CKD in patients with T2D. METHODS: This observational, single-center, cross-sectional study included 360 patients with T2D duration 10 years. Patients with urinary albumin/creatinine ratio (UACR) 3 mg/mmol and estimated glomerular filtration rate (eGFR) 60 ml/min/1.73 m2 were classified as no-CKD group (n=89). Patients with UACR 3 mg/mmol and eGFR 60 ml/min/1.73 m2 formed NA-CKD group (n=111). Individuals with eGFR 60 ml/min/1.73 m2 and UACR mg/mmol 3 were recorded as albuminuric with preserved renal function (A-CKD, n=87). Patients with eGFR 60 ml/min/1.73 m2 and UACR mg/mmol 3 mg/mmol were considered as albuminuric CKD group (A-CKD+, n=73). Urinary nephrin and podocin, the podocyte injury markers, and whey acidic protein four-disulfide core domain protein 2 (WFDC-2), a marker of tubulointerstitial involvement, was assessed by ELISA and compared to control (20 non-diabetic subjects). RESULTS: Age 65 years (p=0.0001), duration of T2D 15 years (p=0.0009), female sex (p=0.04), and therapy with diuretics (p=0.0005) were found as risk factors for NA-CKD. The risk factors for A-CKD were male sex (p=0.01), smoking (p=0.01), waist-to-hip ratio 1 (p=0.01) and HbA1c levels 8% (p=0.005). The duration of T2D 15 years (p=0.01) and the use of dihydropyridine calcium channel blockers (p=0.01) were associated with A-CKD+. In T2D groups, the urinary excretion of nephrin and podocin was increased (all p0.001), more markedly in albuminuric individuals (p0.01 vs. NA-CKD). WFDC-2 excretion was increased in men from all diabetic groups (p0.05) and in women with decreased eGFR only (p0.05 vs. the control and NA-CKD). CONCLUSIONS: The CKD patterns in T2D are heterogeneous according to their clinical and laboratory characteristics. The changes in the excretion of nephrin and podocin indicate the association of albuminuric patterns with podocyte injury. A decrease in eGFR in women with T2D is associated with an increase in urinary excretion of WFDC-2, tubulointerstitial fibrosis marker.

scholarly journals Activation of Rac-1 and RhoA Contributes to Podocyte Injury in Chronic Kidney Disease

PLoS ONE ◽  
2013 ◽  
Vol 8 (11) ◽  
pp. e80328 ◽  
Author(s):  
Andrea Babelova ◽  
Felix Jansen ◽  
Kerstin Sander ◽  
Matthias Löhn ◽  
Liliana Schäfer ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Podocyte Injury

scholarly journals Proteolytic Cleavage by Matriptase Exacerbating Kidney Injury: a Novel Therapeutic Target

2019 ◽  
Author(s):  
Shota Ozawa ◽  
Masaya Matsubayashi ◽  
Hitoki Nanaura ◽  
Motoko Yanagita ◽  
Kiyoshi Mori ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cell Fate ◽  
Therapeutic Target ◽  
Therapeutic Strategy ◽  
Progressive Disease ◽  
Kidney Injury ◽  
Podocyte Injury ◽  
Kidney Glomerulus ◽  
Novel Therapeutic

AbstractChronic kidney disease (CKD) is a progressive disease, and podocyte injury is a potential mechanism. We found that Matriptase was activated at podocytes in CKD patients and mice while a Matriptase inhibitor slowed the progression of mouse kidney disease. The mechanism could be accounted for by an imbalance favoring Matriptase over its cognate inhibitor, hepatocyte growth factor activator inhibitor type 1 (HAI-1), as conditional depletion of HAI-1 in podocytes accelerates podocyte injury. Intriguingly, the N-terminal of Podocin (Podocin-N), as a consequence of Matriptase cleavage of Podocin, translocates to nucleoli. These results suggest that aberrant activation of Matriptase would cause podocyte injury, and a targeting Matriptase could be a novel therapeutic strategy for CKD patients.Significant statementChronic kidney disease (CKD) is a progressive disease. If podocytes, which are specialized cells of the kidney glomerulus that wrap around capillaries, are injured, kidney injury is exacerbated. Thus, a therapeutic strategy to addressing CKD would be to block podocyte injury. The present study provides evidence that Matriptase cleaves Podocin, a component of podocyte slit membrane, and the N-terminal of podocin translocates to nucleoli, causing kidney injury. Our findings show that the N-terminal of Podocin plays an efficient role for cell fate in podocytes. In addition, the inhibition of Matriptase would be a potential therapeutic target for CKD.

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