{Reference Type}: Journal Article
{Title}: Silibinin attenuates TGF-β2-induced fibrogenic changes in human trabecular meshwork cells by targeting JAK2/STAT3 and PI3K/AKT signaling pathways.
{Author}: Wu X;Liang J;Liu J;Huang Y;Zhang L;Liu X;Guo J;Zhang M;Chen Y;Wang J;
{Journal}: Exp Eye Res
{Volume}: 244
{Issue}: 0
{Year}: 2024 Jul 22
{Factor}: 3.77
{DOI}: 10.1016/j.exer.2024.109939
{Abstract}: Transforming growth factor-β2 (TGF-β2) induced fibrogenic changes in human trabecular meshwork (HTM) cells have been implicated in trabecular meshwork (TM) damage and intraocular pressure (IOP) elevation in primary open-angle glaucoma (POAG) patients. Silibinin (SIL) exhibited anti-fibrotic properties in various organs and tissues. This study aimed to assess the effects of SIL on the TGF-β2-treated HTM cells and to elucidate the underlying mechanisms. Our study found that SIL effectively inhibited HTM cell proliferation, attenuated TGF-β2-induced cell migration, and mitigated TGF-β2-induced reorganization of both actin and vimentin filaments. Moreover, SIL suppressed the expressions of fibronectin (FN), collagen type I alpha 1 chain (COL1A1), and alpha-smooth muscle actin (α-SMA) in the TGF-β2-treated HTM cells. RNA sequencing indicated that SIL interfered with the phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB, also known as AKT) signaling pathway, extracellular matrix (ECM)-receptor interaction, and focal adhesion in the TGF-β2-treated HTM cells. Western blotting demonstrated SIL inhibited the activation of Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) and the downstream PI3K/AKT signaling pathways induced by TGF-β2, potentially contributing to its inhibitory effects on ECM protein production in the TGF-β2-treated HTM cells. Our study demonstrated the ability of SIL to inhibit TGF-β2-induced fibrogenic changes in HTM cells. SIL could be a potential IOP-lowering agent by reducing the fibrotic changes in the TM tissue of POAG patients, which warrants further investigation through additional animal and clinical studies.