MicroRNA-302c modulates peritoneal dialysis-associated fibrosis by targeting connective tissue growth factor.

Xiejia Li,Fuyou Liu,Xun Zhou,Yusa Chen,Xinke Yuan,Lin Sun,Yu Liu,Hong Liu,Li Xiao

doi:10.1111/jcmm.14029

Abstract

Long‐term peritoneal dialysis (PD) can lead to the induction of mesothelial/epithelial‐mesenchymal transition (MMT/EMT) and fibrosis; these effects eventually result in ultrafiltration failure and the discontinuation of PD. MicroRNA‐302c (miR‐302c) is believed to be involved in regulating tumour cell growth and metastasis by suppressing MMT, but the effect of miR‐302c on MMT in the context of PD is unknown. MiR‐302c levels were measured in mesothelial cells isolated from the PD effluents of continuous ambulatory peritoneal dialysis patients. After miR‐302c overexpression using lentivirus, human peritoneal mesothelial cell line (HMrSV5) and PD mouse peritoneum were treated with TGF‐β1 or high glucose peritoneal dialysate respectively. MiR‐302c expression level and MMT‐related factors alteration were observed. In addition, fibrosis of PD mouse peritoneum was alleviated by miR‐302c overexpression. Furthermore, the expression of connective tissue growth factor (CTGF) was negatively related by miR‐302c, and LV‐miR‐302c reversed the up‐regulation of CTGF induced by TGF‐β1. These data suggest that there is a novel TGF‐β1/miR‐302c/CTGF pathway that plays a significant role in the process of MMT and fibrosis during PD. MiR‐302c might be a potential biomarker for peritoneal fibrosis and a novel therapeutic target for protection against peritoneal fibrosis in PD patients.

Highlights

Peritoneal dialysis (PD) is one of the most important renal replacement therapies for patients with end‐stage renal failure
Signalling pathways involved in the pathogenesis of peritoneal fibrosis in PD have been studied, these include transforming growth factor‐β1 (TGF‐β1)‐ induced signalling pathways and Toll‐like receptor ligands‐induced signalling pathways.[24,25,26,27]
As the main factor controlling fibrosis in all organs, TGF‐β1 has been demonstrated to play a central role in mesenchymal transition (MMT)

Summary

| INTRODUCTION

Peritoneal dialysis (PD) is one of the most important renal replacement therapies for patients with end‐stage renal failure. Conditions, the peritoneum undergoes structural and functional alterations, which lead to peritoneal fibrosis and ultrafiltration failure; these consequences subsequently limit the long‐ term clinical application of PD.[1] Mesothelial‐to‐mesenchymal transition (MMT) is the initial and reversible process that leads to fibrosis in some organs; because MMT is a source of peritoneal fibroblasts in PD and plays a central role in the peritoneal alterations leading to fibrosis during PD, an increasing number of studies have been carried out to analyse the characteristics of MMT in PD.[2,3,4,5] the mechanism of this process is very complicated, and no effective We have been suggested that that miR‐302c may inhibit TGF‐β1‐induced MMT and fibrosis by suppressing the expression of CTGF

| MATERIALS AND METHODS

| RESULTS

Findings

| DISCUSSION