The study investigated the role of the MAPK/NF-κB pathway in relation to Thymosin β4 and liver fibrosis through a combination of in vivo and in vitro experiments.

The aim of the study was to investigate the mechanism by which Thymosin β4 (Tβ4) ameliorates liver fibrosis, specifically focusing on its role in modulating the MAPK/NF-κB signaling pathway and regulating reactive oxygen species (ROS) levels. The researchers sought to clarify how Tβ4 counteracts liver fibrosis by inhibiting hepatic stellate cell (HSC) activation, proliferation, and migration, thereby providing insights into potential treatment strategies for this condition.

The mouse models for liver fibrosis were established through the procedure of bile duct ligation (BDL). The experiment involved the use mice, which were raised under specific pathogen-free conditions. After the surgery, the mice’s survival status was monitored, and on the 11th day post-operation, the mice were weighed, and their livers were harvested for further analysis.

The overexpression of Tβ4 was found to suppress HSC activation in several ways. Specifically, the study demonstrated that Tβ4 overexpression inhibited the activation of HSCs by reducing markers associated with HSC activation, such as Collagen I, α-Smooth Muscle Actin, and Fibronectin in liver tissues from BDL mouse models.
Tβ4 overexpression in TGF-β1-induced LX-2 cells (a human HSC line) led to significant reductions in cell proliferation and migration abilities. Flow cytometry analysis indicated that Tβ4 caused G0/G1 phase arrest in these cells, decreasing their transition to the S phase and promoting apoptosis.
Successfully suppressed TGF-β1-induced proliferation and migration, showed that Tβ4 acts effectively in managing HSC behaviors that contribute to liver fibrosis.

Overall, the study provided substantial evidence that Tβ4 alleviates liver fibrosis by modulating the MAPK/NF-κB signaling pathway and reducing ROS levels. Tβ4 overexpression has a significant therapeutic effect by impeding HSC activation, thus alleviating liver fibrosis and contributing to potential treatment strategies for liver diseases associated with HSC proliferation and migration.

Full article can be found here: https://doi.org/10.1002/jbt.23338