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 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.

BMSCs alleviate liver cirrhosis by regulating Fstl1/Wnt/β-Catenin signaling pathway

“…As the end stage of liver fibrosis, cirrhosis is also involved in the Wnt/β-Catenin pathway. It has been reported that rat BMSCs alleviate liver fibrosis by inhibiting the Wnt/β-Catenin pathway [ 33 ]. In this study, we used allogeneic mouse BMSCs to treat liver cirrhosis in mice and verified the downregulation of Wnt/β-Catenin protein expression after BMSCs treatment in vivo and in vitro, thus confirming that BMSCs can alleviate the progression of liver cirrhosis through the Wnt/β-Catenin pathway.…”

In Search of a Function for the N6-Methyladenosine in Epitranscriptome, Autophagy and Neurodegenerative Diseases

“…The YTHDF2 could catch eIF4G1 transcripts with m6A methylation, and may induce the mRNA degradation, thereby promoting autophagy [ 76 ]. In addition, the m6A modification could also enhance the stability of zinc finger NFX1-type containing 1 (ZNFX1) antisense RNA 1 (ZFAS1) [ 77 ]. In more detail, for neural cells, the lnc RNA of ZFAS1 is upregulated in neural progenitor cells [ 77 ], which could regulate the expression of ATG10, and control the autophagy by preventing the PI3K/AKT pathway from stimulating the migration and/or proliferation of neural progenitor cells [ 77 ].…”

“…In addition, the m6A modification could also enhance the stability of zinc finger NFX1-type containing 1 (ZNFX1) antisense RNA 1 (ZFAS1) [ 77 ]. In more detail, for neural cells, the lnc RNA of ZFAS1 is upregulated in neural progenitor cells [ 77 ], which could regulate the expression of ATG10, and control the autophagy by preventing the PI3K/AKT pathway from stimulating the migration and/or proliferation of neural progenitor cells [ 77 ]. Similarly, the YTHDF1 could enhance the translation of ATG2A and ATG14 autophagy-related genes by binding to the m6A-modified mRNA of ATG2A and ATG14, consequently assisting autophagy [ 78 ].…”