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.

Possible reason for preferential damage to renal tubular epithelial cells evoked by amphotericin B.

1996 ◽  
Vol 40 (5) ◽  
pp. 1116-1120 ◽  
Author(s):  
I Walev ◽  
S Bhakdi
Keyword(s):  
Epithelial Cells ◽  
Amphotericin B ◽  
Important Determinant ◽  
Major Complication ◽  
Toxic Action ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Recovery Mechanisms ◽  
Renal Tubular

An important determinant of nephrotoxicity, which is the major complication of long-term amphotericin B treatment, is dysfunction of distal tubular epithelial cells. The underlying cause for this rather selective damage to the cells is unknown. In the present investigation, it was shown that kidney epithelial cells were initially damaged by amphotericin B at concentrations of 2.5 to 10 micrograms/ml, as demonstrable by a dramatic drop in cellular K+ levels. Cells could recover from the initial toxic action of the polyene if they were kept in medium of neutral pH, and cellular K+ levels returned to normal after 6 h. However, the recovery mechanisms failed at lower pHs of 5.6 to 6.0. At low pHs, cells became progressively depleted of ATP; they leaked lactate dehydrogenase and became irreversibly damaged after approximately 6 h. The possibility that the low pH characteristic of the distal tubulus lumen renders the renal epithelial cells particularly vulnerable to the toxic action of amphotericin B is raised. The concept is in line with an earlier report that alkalization ameliorates amphotericin B nephrotoxicity in rats.

Mcl-1 is downregulated in cisplatin-induced apoptosis, and proteasome inhibitors restore Mcl-1 and promote survival in renal tubular epithelial cells

2007 ◽  
Vol 292 (6) ◽  
pp. F1710-F1717 ◽  
Author(s):  
Cheng Yang ◽  
Varsha Kaushal ◽  
Sudhir V. Shah ◽  
Gur P. Kaushal
Keyword(s):  
Epithelial Cells ◽  
Cytochrome C ◽  
Caspase 3 ◽  
Proteasome Inhibitors ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Renal Tubular ◽  
Induced Apoptosis

Mcl-1 is an antiapoptotic member of the Bcl-2 family that plays an important role in cell survival. We demonstrate that proteasome-dependent regulation of Mcl-1 plays a critical role in renal tubular epithelial cell injury from cisplatin. Protein levels of Mcl-1 rapidly declined in a time-dependent manner following cisplatin treatment of LLC-PK1cells. However, mRNA levels of Mcl-1 were not altered following cisplatin treatment. Expression of other antiapoptotic members of the Bcl-2 family such as Bcl-2 and BclxL was not affected by cisplatin treatment. Cisplatin-induced loss of Mcl-1 occurs at the same time as the mitochondrial release of cytochrome c, activation of caspase-3, and initiation of apoptosis. Treatment of cells with cycloheximide, a protein synthesis inhibitor, revealed rapid turnover of Mcl-1. In addition, treatment with cycloheximide in the presence or absence of cisplatin demonstrated that cisplatin-induced loss of Mcl-1 results from posttranslational degradation rather than transcriptional inhibition. Overexpression of Mcl-1 protected cells from cisplatin-induced caspase-3 activation and apoptosis. Preincubating cells with the proteasome inhibitor MG-132 or lactacystin not only restored cisplatin-induced loss of Mcl-1 but also resulted in an accumulation of Mcl-1 that exceeded basal levels; however, Bcl-2 and BclxL levels did not change in response to MG-132 or lactacystin. The proteasome inhibitors effectively blocked cisplatin-induced mitochondrial release of cytochrome c, caspase-3 activation, and apoptosis. These studies suggest that proteasome regulation of Mcl-1 is crucial in the cisplatin-induced apoptosis via the mitochondrial apoptotic pathway and that Mcl-1 is an important therapeutic target in cisplatin injury to renal tubular epithelial cells.

Clostridium perfringens epsilon toxin is cytotoxic for human renal tubular epithelial cells

2010 ◽  
Vol 30 (4) ◽  
pp. 275-282 ◽  
Author(s):  
Mariano E. Fernandez Miyakawa ◽  
Osvaldo Zabal ◽  
Claudia Silberstein
Keyword(s):  
Epithelial Cells ◽  
Clostridium Perfringens ◽  
Cell Model ◽  
Cell Damage ◽  
Primary Cultures ◽  
Dependent Manner ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Epsilon Toxin ◽  
Renal Tubular

Clostridium perfringens epsilon toxin (ETX) is responsible for a fatal enterotoxemia in different animal species, producing extensive renal damage, neurological disturbance and edema of lungs, heart and kidneys. However, there is no information about the susceptibility of humans to ETX. Here, we report that primary cultures of human renal tubular epithelial cells (HRTEC) exposed to ETX showed a marked swelling with subsequent large blebs surrounding most cells. The incubation of HRTEC with ETX produced a reduction of cell viability in a dose- and time-dependent manner. The CD50 after 1-hour and 24-hour incubation were 3 µg/mL and 0.5 µg/mL, respectively. The pulse with ETX for 3 min was enough to produce a significant cytotoxic effect on HRTEC after 1-hour incubation. ETX binds to HRTEC forming a large complex of about 160 kDa similar to what was found in the Madin-Darby canine kidney (MDCK) cell line. The HRTEC could be a useful cell model to improve the understanding of the mechanisms involved on the cell damage mediated by ETX.

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 Aldosterone Induces the Proliferation of Renal Tubular Epithelial Cells In Vivo but Not In Vitro

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Juan Hao ◽  
Lingjin Liu ◽  
Ziqian Liu ◽  
Gege Chen ◽  
Yunzhao Xiong ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Cell Proliferation ◽  
Epithelial Cells ◽  
Mtt Assay ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Renal Tubular ◽  
Hk2 Cells

Objective. To investigate the proliferation effect of aldosterone on renal tubular epithelial cells in vivo and in vitro. Methods. Thirty-two male C57BL/6J mice (20–22 g) were divided randomly into four groups: sham, unilateral nephrectomy (UN), unilateral nephrectomy plus aldosterone infusion (UA), and UA plus eplerenone (UAE). The kidneys were removed 6 weeks after treatment. Expression of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry and western blotting. Human kidney proximal tubular epithelial (HK2) and mouse distal convoluted tubule (mDCT) cell lines were stimulated by aldosterone (0, 10−9, 10−8, 10−7, and 10−6 mol/L) in vitro. Cells were collected after 3, 6, 12, 24, 36, and 48 h, and proliferation of each group detected by western blotting, flow cytometry, live imaging, and the MTT assay. In addition, mDCT cells were costimulated with a medium containing a final concentration of 161 mmol/L Na+ and different concentrations of aldosterone, and the number of cells and cellular DNA content was measured by the MTT assay and flow cytometry. Results. Aldosterone could induce a significant increase in the number of PCNA-positive cells in mouse kidneys accompanied by increased deposition of collagen fibers. Eplerenone could inhibit aldosterone-induced cell proliferation and collagen deposition. HK2 cells and mDCT cells administered different concentrations, and different times of aldosterone stimulation failed to cause cell proliferation, and costimulation of aldosterone and salt did not cause proliferation changes in mDCT cells. Conclusions. Aldosterone perfusion can induce proliferation of mouse kidney cells in vivo, and eplerenone can inhibit this change, but aldosterone stimulates HK2 cells and mDCT in vitro without causing their proliferation.

scholarly journals MiR-30c regulates cisplatin-induced apoptosis of renal tubular epithelial cells by targeting Bnip3L and Hspa5

2017 ◽  
Vol 8 (8) ◽  
pp. e2987-e2987 ◽  
Author(s):  
Bin Du ◽  
Xiao-meng Dai ◽  
Shuang Li ◽  
Guo-long Qi ◽  
Guang-xu Cao ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Renal Tubular ◽  
Induced Apoptosis
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