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

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.

• Authors: Xiejia Li, Hong Liu, Lin Sun, Xun Zhou, Xinke Yuan, Yusa Chen, Fuyou Liu, Yu Liu, Li Xiao
• Journal: Journal of cellular and molecular medicine (J Cell Mol Med) Vol. 23 Issue 4 Pg. 2372-2383 (04 2019) ISSN: 1582-4934 [Electronic] England
• PMID: 30693641 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Chemical References

• MIRN302A microRNA, human
• MicroRNAs
• RNA, Messenger
• Transforming Growth Factor beta1
• Connective Tissue Growth Factor

Topics

• Animals
• Connective Tissue Growth Factor (genetics)
• Epithelial Cells (metabolism, pathology)
• Epithelial-Mesenchymal Transition (genetics)
• Gene Expression Regulation (genetics)
• Humans
• Kidney Failure, Chronic (complications, genetics, pathology, therapy)
• Mice
• MicroRNAs (genetics)
• Peritoneal Dialysis (adverse effects)
• Peritoneal Fibrosis (complications, genetics, pathology, therapy)
• Peritoneum (metabolism, pathology)
• RNA, Messenger (genetics)
• Transforming Growth Factor beta1 (genetics)