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

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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.

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