Mechanism of thymosin β4 in ameliorating liver fibrosis via the MAPK/NF-κB pathway

Liver fibrosis is a grievous global challenge, where hepatic stellate cells (HSCs) activation is a paramount step. This study analyzed the mechanism of T beta 4 in ameliorating liver fibrosis via the MAPK/NF-.B pathway. The liver fibrosis mouse models were established via bile duct ligation (BDL) and verified by HE and Masson staining. TGF-beta 1-induced activated LX-2 cells were employed in vitro experiments. T beta 4 expression was determined using RT-qPCR, HSC activation markers were examined using Western blot analysis, and ROS levels were tested via DCFH-DA kits. Cell proliferation, cycle, and migration were examined by CCK-8, flow cytometry, and Transwell assays, respectively. Effects of T beta 4 on liver fibrosis, HSC activation, ROS production, and HSC growth were analyzed after transfection of constructed T beta 4-overexpressing lentiviral vectors. MAPK/NF-.B-related protein levels were tested using Western blotting and p65 expression in the nucleus was detected through immunofluorescence. Regulation of MAPK/NF-.B pathway in TGF-beta 1-induced LX-2 cells was explored by adding MAPK activator U-46619 or inhibitor SB203580. Furthermore, its regulating in liver fibrosis was verified by treating BDL mice overexpressing T beta 4 with MAPK inhibitor or activator. T beta 4 was downregulated in BDL mice. T beta 4 overexpression inhibited liver fibrosis. In TGF-ss 1induced fibrotic LX-2 cells, T beta 4 was reduced and cell migration and proliferation were enhanced with elevated ROS levels, while T beta 4 overexpression suppressed cell migration and proliferation. T beta 4 overexpression blocked the MAPK/NF-.B pathway activation by reducing ROS production, thus inhibiting liver fibrosis in TGF-ss 1 induced LX-2 cells and BDL mice. T beta 4 ameliorates liver fibrosis by impeding the MAPK/NF-.B pathway activation.