scholarly journals MicroRNA-328 Inhibits Renal Tubular Cell Epithelial-to-Mesenchymal Transition by Targeting the CD44 in Pressure-Induced Renal Fibrosis

PLoS ONE ◽  
2014 ◽  
Vol 9 (6) ◽  
pp. e99802 ◽  
Author(s):  
Cheng-Hsien Chen ◽  
Chung-Yi Cheng ◽  
Yen-Cheng Chen ◽  
Yuh-Mou Sue ◽  
Chung-Te Liu ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Mesenchymal Transition ◽  
Renal Tubular

Inhibitory Effect of Gliquidone on Epithelial-to-Mesenchymal-Transition of Renal Tubular Epithelial Cells Under Diabetic Nephropathy Mouse Model

2022 ◽  
Vol 12 (1) ◽  
pp. 71-80
Author(s):  
Ting Liu ◽  
Jie Chen ◽  
Yiying Ying ◽  
Ling Shi ◽  
Zhengyue Chen
Keyword(s):  
Diabetic Nephropathy ◽  
Epithelial Cells ◽  
Body Mass ◽  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Inhibitory Effect ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Mesenchymal Transition ◽  
Renal Tubular

This research aimed to study the inhibitory effect of Glurenorm (gliquidone) on epithelial-to-mesenchymal-transition (EMT) of renal tubular epithelial cells based on the diabetic nephropathy (DN) model. In this study, 30 specific pathogen-free (SPF) mice were selected to construct DN model and randomly rolled into groups A, B, and C, with 10 mice in each group. Low-dose, mediumdose, and high-dose Glurenorm were administered intragastrically. The results showed that the serum urea nitrogen content (7.23±0.39 mmol/L, 6.18±0.46 mmol/L) of control and C group was considerably inferior to A group (8.01±0.48 mmol/L), and the content of C group was greatly lower than controls (P < 0.05). The creatinine clearance rate (2.97±0.44 mL/min, 4.02±0.31 mL/min) of mice in control and C group was notably superior to A group (2.18±0.38 mL/min), and that of C group was obviously higher versus controls (P < 0.05). After 5 weeks of intragastric intervention by Glurenorm, the body mass of the mice in control and C group was evidently lower relative to A group, and that of C group was obviously higher versus controls (P < 0.05). Mice in control and C group were remarkably lower in body mass at the 7th week after Glurenorm intervention versus A group, and C group was relatively lower versus controls (P < 0.05). In short, EMT played an important role in promoting the occurrence and progression of renal fibrosis. Glurenorm can reduce the progression of renal fibrosis, inhibit EMT of renal tubular epithelial cells, and effectively protect kidney function.

The miR-200 family regulates TGF-β1-induced renal tubular epithelial to mesenchymal transition through Smad pathway by targeting ZEB1 and ZEB2 expression

2012 ◽  
Vol 302 (3) ◽  
pp. F369-F379 ◽  
Author(s):  
Mingxia Xiong ◽  
Lei Jiang ◽  
Yang Zhou ◽  
Wenjing Qiu ◽  
Li Fang ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Expression Profiles ◽  
Renal Tubules ◽  
Dependent Manner ◽  
Mesenchymal Transition ◽  
Renal Tubular ◽  
Novel Therapeutic Strategies ◽  
Tgf Β1

Most chronic kidney injuries inevitably progress to irreversible renal fibrosis. Tubular epithelial-to-mesenchymal transition (EMT) is recognized to play pivotal roles in the process of renal fibrosis. However, a comprehensive understanding of the pathogenesis of renal scar formation and progression remains an urgent task for renal researchers. The endogenously produced microRNAs (miRNAs), proved to play important roles in gene regulation, probably regulate most genes involved in EMT. In this study, we applied microarray analysis to investigate the expression profiles of miRNA in murine interstitial fibrotic kidneys induced by unilateral ureteral obstruction (UUO). It was found that miR-200a and miR-141, two members of the miR-200 family, were downregulated at the early phase of UUO. In TGF-β1-induced tubular EMT in vitro, it was also found that the members of the miR-200 family were downregulated in a Smad signaling-dependent manner. It was demonstrated that the miR-200 family was responsible for protecting tubular epithelial cells from mesenchymal transition by target suppression of zinc finger E-box-binding homeobox (ZEB) 1 and ZEB2, which are E-cadherin transcriptional repressors. The results suggest that downregulation of the miR-200 family initiates the dedifferentiation of renal tubules and progression of renal fibrosis, which might provide important targets for novel therapeutic strategies.

scholarly journals Gasdermin E Deletion Attenuates Ureteral Obstruction- and 5/6 Nephrectomy-Induced Renal Fibrosis and Kidney Dysfunction

2021 ◽  
Vol 9 ◽  
Author(s):  
Mengying Wu ◽  
Weiwei Xia ◽  
Qianqian Jin ◽  
Anning Zhou ◽  
Qian Wang ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Caspase 3 ◽  
Inflammatory Responses ◽  
Kidney Diseases ◽  
Tubular Cell ◽  
Renal Tubular Cell ◽  
Kidney Dysfunction ◽  
Renal Tubular

Renal fibrosis contributes to kidney dysfunction in various chronic kidney diseases (CKDs). Renal fibrosis can be driven by renal tubular cell death and inflammation. Deletion of gasdermin E (GSDME), an executor of pyroptosis, has been reported to suppress renal tubular cell pyroptosis in several models of kidney injury. However, additional evidence confirming the role of GSDME in regulating renal fibrosis and kidney function in different CKDs is required. In our study, N-GSDME expression was significantly elevated in CKD models in vivo and in vitro. GSDME deletion alleviated renal fibrosis and inflammation in both unilateral ureteral ligation (UUO) and 5/6 nephrectomy (5/6Nx) models along with the attenuation of renal dysfunction. N-GSDME overexpression had a detrimental effect on fibrotic responses in UUO kidneys and TGF-β1-treated renal tubular epithelial cells. In addition, administration of caspase-3 inhibitor Z-DEVD-FMK, which inhibits caspase-3-mediated GSDME cleavage, protected against renal fibrosis both in vivo and in vitro. Collectively, these results provide evidence that the activation of GSDME is critical in regulating both renal fibrosis and kidney dysfunction possibly via promoting inflammatory responses in CKD. These findings may offer new insights into the identification of new therapeutic targets for protecting against CKDs.

scholarly journals Metformin Improves Epithelial-to-Mesenchymal Transition Induced by TGF-β1 in Renal Tubular Epithelial NRK-52E Cells via Inhibiting Egr-1

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Meiping Guan ◽  
Wenqi Li ◽  
Lingling Xu ◽  
Yanmei Zeng ◽  
Dan Wang ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Transforming Growth Factor ◽  
Mesenchymal Transition ◽  
Early Growth Response ◽  
Real Time Quantitative Pcr ◽  
Novel Target ◽  
Renal Tubular ◽  
Tgf Β1 ◽  
E Cadherin

The early growth response- (Egr-) 1 has been found to play a key role in organ fibrosis. Metformin has been shown to be effective in attenuating renal tubular epithelial-to-mesenchymal transition (EMT), which is involved in renal fibrosis. However, it is unknown whether metformin improves EMT via inhibiting Egr-1. In this study, rat renal tubular epithelial (NRK-52 E) cells, treated by transforming growth factor- (TGF-)β1 of 10 ng/ml with or without metformin of 1 mmol/l, were transfected by siEgr-1 or M61-Egr-1 plasmids to knock down or overexpress Egr-1, respectively. The gene and protein expressions of E-cadherin,α-SMA, fibronectin (FN), and Egr-1 were determined by real-time quantitative PCR and Western blotting, respectively. We observed that TGF-β1 significantly reduced E-cadherin expression and upregulated the expressions of FN,α-SMA, and Egr-1, which can be reversed by metformin. M61-Egr-1 transfection could exacerbate EMT, which can be reversed by metformin. Taken together, our data show that Egr-1 plays an important role in TGF-β1-induced EMT of renal tubular epithelial cells and metformin improves EMT while inhibiting Egr-1, which provides a potential novel target to combat renal fibrosis.

scholarly journals PAX2 regulates NRP-1 expression in renal tubular epithelial cellsto promote epithelial-to-mesenchymal transition and renal fibrosis

2018 ◽  
Vol 2 (1) ◽  
Author(s):  
Ling Hou ◽  
Yue Du ◽  
Chengguang Zhao ◽  
Xiuli Wang ◽  
Yubin Wu
Keyword(s):  
Western Blot ◽  
Real Time ◽  
Real Time Pcr ◽  
Renal Fibrosis ◽  
Epithelial To Mesenchymal Transition ◽  
Vector Group ◽  
Mesenchymal Transition ◽  
Empty Vector ◽  
Renal Tubular ◽  
E Cadherin

To observe the expression of neuropilin-1 (NRP-1) induced by paired-box gene 2 (PAX2) during the process of epithelial-to-mesenchymal transition (EMT) and renal fibrosis in unilateral ureteral obstruction (UUO) model in rats, and explore the mechanism of EMT induced by PAX2. Methods: The recombinant lentivirus expression vector for PAX2 was constructed and transfected into rat normal renal tubular epithelial cell line (NRK52E). The experimental cells were divided into three groups: transfection group, empty vector group, and normal group. E-cadherin and α-SMA were detected by western blot and real-time PCR. Expression of NRP-1 was detected by western blot, real-time PCR, and immunofluorescence. Sixty male Wistar rats were randomly divided into two groups: the sham-operation group (n=30) underwent left ureteral dissection, the UUO group (n=30) underwent left ureteral ligation. Post-operation on days 3, 7, 14, 21 and 28, 6 rats from each of the groups were sacrificed and the obstructed kidneys were dissected out. The histopathological changes were observed by hematoxylin-eosin and Masson staining. E-cadherin and α-SMA were detected by western blot and immunohistochemistry. Expression of NRP-1 and PAX2 were determined by western blot, immunohistochemistry, and real-time PCR. Results: Expression of NRP-1 mRNA and protein and α-SMA protein increased (P<0.05) while E-cadherin protein expression decreased (P<0.05) in the transfection group as compared to the empty vector group in vitro. In the UUO group, fibrosis was obvious, and there was decreased expression of E-cadherin protein (P<0.05) and increased expression of α-SMA protein and NRP-1 mRNA and protein (P<0.05) in comparison to the sham group. Conclusion: NRP-1 maybe mediate PAX2-induced EMT in renal tubular epithelial cells and renal fibrosis.

scholarly journals AT1 and AT2 receptors modulate renal tubular cell necroptosis in angiotensin II-infused renal injury mice

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Yongjun Zhu ◽  
Hongwang Cui ◽  
Jie Lv ◽  
Haiqin Liang ◽  
Yanping Zheng ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Renal Injury ◽  
Critical Role ◽  
Kidney Injury ◽  
Renin Angiotensin System ◽  
Tubular Cell ◽  
Tubular Damage ◽  
Renal Tubular Cell ◽  
Ang Ii ◽  
Renal Tubular

AbstractAbnormal renin-angiotensin system (RAS) activation plays a critical role in the initiation and progression of chronic kidney disease (CKD) by directly mediating renal tubular cell apoptosis. Our previous study showed that necroptosis may play a more important role than apoptosis in mediating renal tubular cell loss in chronic renal injury rats, but the mechanism involved remains unknown. Here, we investigate whether blocking the angiotensin II type 1 receptor (AT1R) and/or angiotensin II type 2 receptor (AT2R) beneficially alleviates renal tubular cell necroptosis and chronic kidney injury. In an angiotensin II (Ang II)-induced renal injury mouse model, we found that blocking AT1R and AT2R effectively mitigates Ang II-induced increases in necroptotic tubular epithelial cell percentages, necroptosis-related RIP3 and MLKL protein expression, serum creatinine and blood urea nitrogen levels, and tubular damage scores. Furthermore, inhibition of AT1R and AT2R diminishes Ang II-induced necroptosis in HK-2 cells and the AT2 agonist CGP42112A increases the percentage of necroptotic HK-2 cells. In addition, the current study also demonstrates that Losartan and PD123319 effectively mitigated the Ang II-induced increases in Fas and FasL signaling molecule expression. Importantly, disruption of FasL significantly suppressed Ang II-induced increases in necroptotic HK-2 cell percentages, and necroptosis-related proteins. These results suggest that Fas and FasL, as subsequent signaling molecules of AT1R and AT2R, might involve in Ang II-induced necroptosis. Taken together, our results suggest that Ang II-induced necroptosis of renal tubular cell might be involved both AT1R and AT2R and the subsequent expression of Fas, FasL signaling. Thus, AT1R and AT2R might function as critical mediators.

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