Liu Zhaoguo, Zhou Song, Zhang Ya, Zhao Ming
The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
Liuzhou Worker's Hospital, Liuzhou, Guangxi Province, China.
Infect Agent Cancer. 2022 Apr 19;17(1):17. doi: 10.1186/s13027-022-00432-4.
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.
After the rat liver fibrosis model was induced by continuous injection of carbon tetrachloride (CCl), 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).
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.
Our data suggested that BMSCs exerted antifibrotic effects by activating the expression of GSK3β and inhibiting the Wnt3a/β-catenin signalling pathway.
骨髓间充质干细胞（BMSCs）可有效减轻肝纤维化，肝纤维化是由各种慢性肝病引起的一种病理损伤。本研究旨在探讨BMSCs的抗纤维化作用，并阐明BMSCs在体外和体内影响肝纤维化的潜在机制。
通过连续注射四氯化碳（CCl）诱导大鼠肝纤维化模型后，给予BMSCs治疗4周，并进行组织病理学分析和肝功能检测。用转化生长因子-β1（TGF-β1）刺激肝星状细胞系（HSC-T6细胞），并通过CCK-8法、流式细胞术、实时聚合酶链反应（PCR）、蛋白质免疫印迹法和酶联免疫吸附测定（ELISA）分析细胞的活化和增殖情况。
我们的数据表明，BMSCs可有效减少体内胶原蛋白的积累，增强肝功能并改善肝纤维化。BMSCs增加了HSC-T6细胞中的亚G1期细胞群。此外，与BMSCs共培养可降低HSC-T6细胞中α-平滑肌肌动蛋白（α-SMA）、I型胶原蛋白、细胞周期蛋白D1和c-Myc的表达，并激活糖原合成酶激酶3β（GSK3β）的磷酸化。GSK3β抑制剂SB216763可逆转BMSCs的作用。Wnt/β-连环蛋白信号通路参与了BMSCs介导的对HSC-T6细胞活化的抑制作用。
我们的数据表明，BMSCs通过激活GSK3β的表达并抑制Wnt3a/β-连环蛋白信号通路发挥抗纤维化作用。
