Rat bone marrow mesenchymal stem cells (BMSCs) inhibit liver fibrosis by activating GSK3β and inhibiting the Wnt3a/β-catenin pathway

Abstract

Abstract Background Bone marrow mesenchymal stem cells (BMSCs) can effectively alleviate liver fibrosis, which is a pathological injury caused by various chronic liver diseases. This study aimed to investigate the antifibrotic effects of BMSCs and elucidate the underlying mechanism by which BMSCs affect liver fibrosis in vitro and in vivo. Methods After the rat liver fibrosis model was induced by continuous injection of carbon tetrachloride (CCl4), BMSCs were administered for 4 weeks, and histopathological analysis and liver function tests were performed. T6 hepatic stellate cells (HSC-T6 cells) were stimulated by TGF-β1, and the activation and proliferation of cells were analyzed by CCK-8 assays, flow cytometry, real-time PCR, western blotting and enzyme-linked immunosorbent assay (ELISA). Results Our data demonstrated that BMSCs effectively reduced the accumulation of collagen, enhanced liver functionality and ameliorated liver fibrosis in vivo. BMSCs increased the sub-G1 population in HSC-T6 cells. In addition, coculture with BMSCs reduced the expression of α-SMA, collagen I, cyclin-D1, and c-Myc in HSC-T6 cells and activated the phosphorylation of GSK3β. The GSK3β inhibitor SB216763 reversed the effect of BMSCs. The Wnt/β-catenin signalling pathway was involved in BMSC-mediated inhibition of HSC-T6 cell activation. Conclusions Our data suggested that BMSCs exerted antifibrotic effects by activating the expression of GSK3β and inhibiting the Wnt3a/β-catenin signalling pathway.