LGALS3 promotes liver fibrosis by enhancing the expression and phosphorylation of ERK1/2

Background: Liver fibrosis represents the common endpoint of numerous chronic liver diseases. Current therapeutic approaches predominantly focus on alleviating symptoms or addressing the underlying causes, with limited options available for reversing fibrosis. Existing antifibrotic drugs often exhibit low efficacy and carry significant side effects, underscoring the urgent need for novel therapeutic targets. LGALS3, a β-galactoside-binding lectin, participates in inflammation and fibrosis across multiple organs. However, its specific role in liver fibrosis remains poorly understood. This study endeavors to elucidate the cellular and molecular mechanisms by which LGALS3 regulates liver fibrosis and assess its potential as a therapeutic target. Subjects and Methods: To clarify the role of LGALS3 in liver fibrosis, a TGF-β1-induced liver fibrosis model was established, and the expression level of LGALS3 was analyzed. LGALS3 overexpression and knockdown cell lines were constructed in LX-2 cell line. RT-qPCR, western blot, CCK8 assay, and wound healing assay were employed to investigate the impact of LGALS3 on LX-2 cell activation, proliferation, migration, and the ERK1/2 pathway. In the LGALS3 overexpression cell model, PD98059 intervention was applied to mimic the therapeutic effect on liver fibrosis. Results: LGALS3 overexpression significantly promoted the proliferation and migration of LX-2 cells, along with the expression and phosphorylation of ERK1/2. Conversely, LGALS3 knockdown and treatment with the PD98059 inhibitor reduced LX-2 cell proliferation and migration, as well as the expression and phosphorylation of ERK1/2. Conclusions: This study has clarified the pivotal regulatory role of the LGALS3-ERK1/2 signaling axis in liver fibrosis, uncovering novel molecular mechanisms underlying the activation, proliferation, and migration of hepatic stellate cells. These findings enhance our understanding of the pathological process of liver fibrosis, suggesting that targeting the LGALS3-ERK1/2 axis may serve as a novel therapeutic strategy for intervening in liver fibrosis. It also provides potential targets and innovative directions for the development of anti-liver fibrosis drugs.