Overexpressed miR‐486 in bone marrow mesenchymal stem cells represses urethral fibrosis and targets Col13a1 in urethral stricture rats

Abstract

Urethral stricture (US) is a challenging problem in urology and its pathogenesis of US is closely related to the fibrotic process. Previous evidence has indicated the downregulation of microRNA (miR)‐486 in injured urethral specimens of rats. This study aimed to explore the effects of miR‐486‐overexpressed bone marrow mesenchymal stem cells (BMSCs) on US. BMSCs were identified by detecting their multipotency and surface antigens. Lentivirus virus expressing miR‐486 was transduced into rat BMSCs to overexpress miR‐486. Transforming growth factor (TGF)‐β1 induced fibrotic phenotypes in urethral fibroblasts (UFs) and rat models. Western blotting showed protein levels of collagen I/III and collagen type XIII alpha 1 chain (Col13a1). Real time quantitative polymerase chain reaction was utilized for messenger RNA level evaluation. Hematoxylin‐eosin, Masson's trichrome, and Von Willebrand Factor staining were conducted for histopathological analysis. Immunofluorescence staining was employed for detecting alpha smooth muscle actin (α‐SMA) expression. Luciferase reporter assay verified the interaction between miR‐486 and Col13a1. The results showed that miR‐486‐overexpressed BMSCs suppressed collagen I/III and α‐SMA expression in TGF‐β1‐stimulated UFs. miR‐486‐overexpressed BMSCs alleviated urethral fibrosis, collagen deposition, and epithelial injury in the urethral tissue of US rats. miR‐486 targeted and negatively regulated Col13a1 in US rats. In conclusion, overexpression of miR‐486 in BMSCs targets Col13a1 and attenuates urethral fibrosis in TGF‐β1‐triggered UFs and US rats.