MiR-200a negatively regulates TGF-β1-induced epithelial-mesenchymal transition of peritoneal mesothelial cells by targeting ZEB1/2 expression

Author:

Guo Runsheng1,Hao Guojun23,Bao Yi2,Xiao Jun2,Zhan Xiaojiang2,Shi Xintian2,Luo Laimin2,Zhou Jing2,Chen Qinkai2,Wei Xin2

Affiliation:

1. Department of Orthopedics, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

2. Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

3. Department of Nephrology, Zhongshan City People’s Hospital/Zhongshan Hospital of Sun Yat-sen University, Zhongshan, Guangdong, China

Abstract

Although epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells was recognized as the key process of peritoneal fibrosis, which is a major cause of peritoneal failure related to peritoneal dialysis (PD), mechanisms underlying these processes remain largely unknown. In this study, we found that miR-200a was significantly downregulated in peritoneal tissues with fibrosis in a rat model of PD. In vitro, transforming growth factor (TGF)-β1-induced EMT, identified by de novo expression of α-smooth muscle actin and a loss of E-cadherin in human peritoneal mesothelial cells (HPMCs), was associated with downregulation of miR-200a but upregulation of zinc finger E-box-binding homeobox 1/2 (ZEB1/2), suggesting a close link between miR-200a and ZEB1/2 in TGF-β1-induced EMT. It was further demonstrated that miR-200a was able to bind to the 3′UTR of ZEB1/2, and overexpression of miR-200a blocked TGF-β1-induced upregulation of ZEB1/2 and, therefore, inhibited EMT and collagen expression. In contrast, overexpression ZEB1/2 blocked miR-200a inhibition of EMT and collagen expression in HMPCs. In conclusion, miR-200a could negatively regulate TGF-β1-induced EMT by targeting ZEB1/2 in peritoneal mesothelial cells. Blockade of EMT in HPMCS indicates the therapeutic potential of miR-200a as a treatment for peritoneal fibrosis associated with PD.

Funder

National Nature Science Foundation of China

Publisher

American Physiological Society

Subject

Physiology

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