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

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 anti-fibrosis role of BMSCs and illuminate the underlying mechanism of BMSCs on liver fibrosis in vitro and vivo.Methods: After the rat liver fibrosis models were induced by continuous injection of carbon tetrachloride (CCl4), BMSCs were administered for 4 weeks and the histopathological analysis and liver function tests were performed. HSC-T6 was stimulated by TGF-β1, the activation and proliferation of cells were detected by MTT, flow cytometry, western blotting and cellular immunofluorescence assays.Results: Our data demonstrated that BMSCs effectively reduced the accumulation of collagen, enhanced liver functionality and liver fibrosis in vivo. BMSCs increased sub G1 population in HSC-T6. In addition, co-cultured with BMSCs, the expression of α-SMA, collagen I, cyclin-D1, c-Myc in HSC-T6 were reduced, and activated phosphorylation of GSK3β. SB216763, an inhibitor of GSK3β, reversed the effect of BMSCs. It was also found the Wnt/β-catenin signaling pathway was involved in HSC-T6 activation inhibition by BMSCs. Conclusions: Our data suggested that BMSCs treatment exerted antifibrotic effects via activating the expression of GSK3β and inhibiting the Wnt3a/β-catenin signaling pathway.