PMID- 35440002 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220716 IS - 1750-9378 (Print) IS - 1750-9378 (Electronic) IS - 1750-9378 (Linking) VI - 17 IP - 1 DP - 2022 Apr 19 TI - Rat bone marrow mesenchymal stem cells (BMSCs) inhibit liver fibrosis by activating GSK3beta and inhibiting the Wnt3a/beta-catenin pathway. PG - 17 LID - 10.1186/s13027-022-00432-4 [doi] LID - 17 AB - 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 (CCl(4)), 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-beta1, 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 alpha-SMA, collagen I, cyclin-D1, and c-Myc in HSC-T6 cells and activated the phosphorylation of GSK3beta. The GSK3beta inhibitor SB216763 reversed the effect of BMSCs. The Wnt/beta-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 GSK3beta and inhibiting the Wnt3a/beta-catenin signalling pathway. CI - (c) 2022. The Author(s). FAU - Liu, Zhaoguo AU - Liu Z AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China. AD - Liuzhou Worker's Hospital, Liuzhou, Guangxi Province, China. FAU - Zhou, Song AU - Zhou S AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China. FAU - Zhang, Ya AU - Zhang Y AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China. FAU - Zhao, Ming AU - Zhao M AD - The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China. zhaoming02@hotmail.com. AD - Department of Organ Transplantation, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510280, Guangdong Province, China. zhaoming02@hotmail.com. LA - eng PT - Journal Article DEP - 20220419 PL - England TA - Infect Agent Cancer JT - Infectious agents and cancer JID - 101276559 PMC - PMC9017036 OTO - NOTNLM OT - BMSCs OT - GSK3beta OT - Hepatic stellate cells OT - Liver fibrosis OT - Wnt/beta-catenin pathway COIS- The authors declare that they have no competing interests. EDAT- 2022/04/21 06:00 MHDA- 2022/04/21 06:01 PMCR- 2022/04/19 CRDT- 2022/04/20 05:08 PHST- 2022/02/24 00:00 [received] PHST- 2022/04/11 00:00 [accepted] PHST- 2022/04/20 05:08 [entrez] PHST- 2022/04/21 06:00 [pubmed] PHST- 2022/04/21 06:01 [medline] PHST- 2022/04/19 00:00 [pmc-release] AID - 10.1186/s13027-022-00432-4 [pii] AID - 432 [pii] AID - 10.1186/s13027-022-00432-4 [doi] PST - epublish SO - Infect Agent Cancer. 2022 Apr 19;17(1):17. doi: 10.1186/s13027-022-00432-4.