scholarly journals KIM-1 Mediates High Glucose-Induced Autophagy and Apoptosis in Renal Tubular Epithelial Cells

2016 ◽  
Vol 38 (6) ◽  
pp. 2479-2488 ◽  
Author(s):  
Rong Gou ◽  
Juntong Chen ◽  
Shifeng Sheng ◽  
Ruiqiang Wang ◽  
Yudong Fang ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Flow Cytometry ◽  
Epithelial Cells ◽  
High Glucose ◽  
Kidney Injury ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Normal Glucose ◽  
Renal Tubular

Background/Aim: To investigate the role of kidney injury molecular 1 (KIM-1) in high glucose-induced autophagy and apoptosis in renal tubular epithelial cells. Methods: Human renal tubular epithelial cells (HK2) were treated with normal glucose (NG, D -glucose 5.6 mmol/L), high glucose (HG, 30 mmol/L), high osmotic (HO, D-glucose 5.6 mmol/L + D-mannitol 24.4 mmol/L), HG + KIM-1 siRNA, HG + siRNA control. The expressions of KIM-1 and microtubule-associated protein 1 light chain 3II (LC3II) were measured by western blot as well as real time PCR; the number of autophagosome was detected by electron microscopy; and the level of apoptosis was analyzed by flow cytometry. Results: In the HG group, the expressions of KIM-1 and LC3II were increased markedly, which was accompanied by more autophagosome and higher level of apoptosis compared with NG group. Silencing of KIM-1 by siRNA inhibited the increases in the levels of LC3II, autophagosome and apoptosis. Conclusion: KIM-1 may mediate high glucose-induced autophagy and apoptosis in renal tubular epithelial cells.

scholarly journals Activation of GSDMD contributes to acute kidney injury induced by cisplatin

2020 ◽  
Vol 318 (1) ◽  
pp. F96-F106 ◽  
Author(s):  
Yuanyuan Li ◽  
Weiwei Xia ◽  
Mengying Wu ◽  
Jie Yin ◽  
Qian Wang ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Epithelial Cells ◽  
Antitumor Agents ◽  
Active Form ◽  
Elevated Serum ◽  
Kidney Injury ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Renal Tubular

Cisplatin is one of the most effective antitumor agents, but its clinical use is highly limited by its severe side effects, especially nephrotoxicity. Recently, the active form of gasdermin D (GSDMD), termed GSDMD-N, was identified to mediate pyroptotic inflammatory cell death in several diseases. However, the role of the GSDMD-N fragment in cisplatin-induced acute kidney injury (AKI) remains unclear. In the present study, we found that pyroptosis was induced by cisplatin in both mouse kidney tissues and renal tubular epithelial cells, accompanied by increased expression of the GSDMD-N fragment. In GSDMD knockout mice with cisplatin-induced AKI, we found that cisplatin-induced loss of renal function, renal tubular injury, and inflammation was significantly attenuated compared with wild-type mice. Furthermore, the GSDMD-N fragment was overexpressed by an established rapid plasmid tail vein injection approach to evaluate the role of this cleaved form of GSDMD in AKI. As expected, mice with GSDMD-N fragment overexpression in the kidney were more susceptible to cisplatin-induced AKI than control mice, as evidenced by further elevated serum levels of blood urea nitrogen and creatinine, aggravated renal pathology, increased expression of neutrophil gelatinase-associated lipocalin and kidney injury molecule-1, and enhanced renal inflammatory cytokine secretion, which indicates a pathogenic role of GSDMD-N in cisplatin-induced AKI by triggering cell pyroptosis. Similar results were also observed in renal tubular epithelial cells overexpressing the GSDMD-N fragment. Thus these findings suggested that the activation of GSDMD contributes to cisplatin-induced AKI, possibly through triggering pyroptosis.

Functional Role of SUV39H1 in Human Renal Tubular Epithelial Cells Under High-glucose Ambiance

Inflammation ◽  
2017 ◽  
Vol 41 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Jiayi Wang ◽  
Wenzhe Yan ◽  
Xiaofei Peng ◽  
Yafeng Jiang ◽  
Liyu He ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
High Glucose ◽  
Functional Role ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Renal Tubular

scholarly journals BAFF signaling drives interstitial transformation of mouse renal tubular epithelial cells in a Pin1-dependent manner

2021 ◽  
Author(s):  
Haiyan Xu ◽  
Dan Song ◽  
Renfang Xu ◽  
Xiaozhou He
Keyword(s):  
Flow Cytometry ◽  
Epithelial Cells ◽  
Biological Activities ◽  
High Dose ◽  
Dependent Manner ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Aberrant Expression ◽  
Renal Tubular

AbstractAberrant expression of B cell–activating factor belonging to TNF superfamily (BAFF) and its receptors results in abnormal biological activities in hematopoietic and non-hematopoietic cells and is closely associated with the occurrence and development of various diseases. However, the biological significance and potential mechanisms underlying BAFF signaling in renal tubular epithelial cells (RTECs) remain unknown. This study aimed to investigate the biological role of BAFF signaling in RTECs. Mice primary RTECs were applied. The proliferation status and apoptotic rates were examined by MTS assay and flow cytometry, respectively. The expression of BAFF and its receptors was analyzed via flow cytometry and sodium ion transport function, and cytokeratin-18 expression was detected through immunofluorescence staining. In addition, Pin1 was knocked down via siRNA and its expression was assessed through reverse transcription PCR. Lastly, western blotting was performed to analyze E-cadherin, ɑ-SMA, and Pin1 expression. Results suggested that BAFF-R was significantly upregulated upon IFN-γ stimulation, and enhancement of BAFF signaling promoted cell survival and reduced their apoptotic rate, while simultaneously reducing the epithelial phenotype and promoting the interstitial transformation of cells. Furthermore, Pin1 was significantly increased, along with the upregulation of BAFF signaling in the RTECs, and participated in interstitial transformation induced by BAFF signaling. Collectively, the present results elucidate the potential mechanism of loss of normal function of RTECs under long-term high dose of BAFF stimulation provides a potential therapeutic target for renal interstitial fibrosis, and underlining mechanisms of shortening of long-term outcomes of kidney allografts via augmenting of BAFF signaling.

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