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

Abstract

Background. Long-term PD can lead to induction of mesothelial/epithelial–mesenchymal transition (MMT/EMT) and fibrosis, eventually leading to ultrafiltration failure and discontinuation of PD. MicroRNA-302c (miR-302c) is believed to be involved in regulating tumor cells growth and metastasis by suppressing MMT, but the effect of miR-302c on MMT relevant to PD is unknown. Methods. MiR-302c was assayed in mesothelial cells isolated from PD effluent of stable PD patients. MiR-302c was overexpressed in human peritoneal mesothelial cell line (HMrSV5) and PD mouse peritoneum by lentivirus, and then were subjected to transforming growth factor β1 (TGF-β1) or high glucose peritoneal dialysis fluid-induced peritoneal fibrosis. Results. The altered expression of miR-302c was accompanied with alterations in MMT-related factors. In HMrSV5 treated with TGF-β1, the decreased E-cadherin and increased α-SMA、collagen I expression were reversed by overexpression of miR-302c, and the fibrotic morphologic changes in PD mouse peritoneum were alleviated. Furthermore, the expression of connective tissue growth factor (CTGF) was negatively related with miR-302c, and LV-miR-302c can reverse the upregulation of CTGF induced by TGF-β1. Conclusions. These data suggest that there is a novel TGF-β1/miR-302c/CTGF pathway that has 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 of peritoneal fibrosis protection in PD patients.