Mesoderm/mesenchyme homeobox l as a potential target that orchestrates hepatic stellate cell activation

Aim: Hepatic stellate cell (HSC) activation is considered as a key event during the occurrence of liver fibrosis. Recent studies have shown that Mesoderm/mesenchyme homeobox l (Meox1) can promote organ fibrosis, such as in the skin and heart. We aimed to elucidate a potential role of the Meox1 during Hepatic stellate cell (HSC) activation. Methods: : The human HSC cell line Lx-2 was employed as model to evaluate the function of Meox1 in HSC activation. The expression of fibrotic genes was measured, and proliferation, migration, cell cycle assays were performed. Results: : In this study, Meox1 was recognized as a positive regulated factor of HSC activation. Following transforming growth factor-β1 (TGF-β1)-treated Lx-2 cells, the expression level of Meox1 was upregulated significantly. Meox1 knockdown mediated by small interference RNA (siRNA) was observed to inhibit TGF-β1-induced expression of HSC activation markers and fibrotic genes, including α smooth muscle actin (α-SMA), collagen type I (collagen-I) and matrix metalloproteinase 2 (MMP-2). Overexpression of Meox1 promoted HSC activation, as demonstrated by an increase in specific markers, including α-SMA, collagen-I and MMP-2 and enhancement of proliferation and migration. We also found that phosphorylation of Smad3 was elevated with forced expression of Meox1 in Lx-2 cells, whereas the TGF-β1 and total Smad3 protein levels were not changed. In addition, Meox1 could induce extension of the G1 phase and expression of the p21 CIP1/WAF1 in Lx-2 cells. Conclusions: : Our results indicate that Meox1 could play a crucial role in HSC activation and potential participation in the canonical TGF-β1/Smad pathway.