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

BACKGROUND

Hepatic stellate cell (HSC) activation is a critical factor in the development of liver fibrosis. Recent research indicates that mesoderm/mesenchyme homeobox 1 (Meox1) contributes to fibrosis in organs like the skin and heart.

OBJECTIVES

To investigate the potential impact of Meox1 on HSC activation and provide an available target for hepatic fibrosis research.

MATERIAL AND

METHODS

The human HSC cell line LX-2 was utilized to investigate the role of Meox1 in HSC activation. Fibrotic gene expression was analyzed, and assays were conducted to assess cell proliferation, migration and the cell cycle.

RESULTS

Meox1 was identified as a positive regulator of HSC activation. We found that transforming growth factor-β1 (TGF-β1) treatment significantly upregulated Meox1 expression in a dose-dependent manner in LX-2 cells, and the expression levels of α-smooth muscle actin (α-SMA), collagen type I (collagen-I) and matrix metalloproteinase-2 (MMP-2) also increased progressively with higher concentrations of TGF-β1. Knockdown of Meox1 via small interfering RNA (siRNA) inhibited TGF-β1-induced expression of HSC activation markers and fibrotic genes, including α-SMA, collagen-I and MMP-2. Conversely, Meox1 overexpression promoted HSC activation, evidenced by increased levels of α-SMA, collagen-I and MMP-2. Meanwhile, Meox1 overexpression accelerated cell proliferation and enhanced cell migration. Additionally, forced expression of Meox1 in LX-2 cells elevated Smad3 phosphorylation level, although TGF-β1 and total Smad3 protein levels remained unchanged. Furthermore, we observed that Meox1 could induce a redistribution of the cell population, extending the G1 phase, and that Meox1-upregulated p21CIP1/WAF1 expression in LX-2 cells was independent of p53.

CONCLUSIONS

Our findings suggest that Meox1 plays a pivotal role in HSC activation and may be involved in the canonical TGF-β1/Smad pathway.