The transcription factor mesenchyme homeobox 1 exacerbates hepatic fibrosis by transcriptional activation of connective tissue growth factor

Abstract

As a chronic condition, liver fibrosis is characterized by diverse etiological factors, and the pivotal event to its pathogenesis is the activation of quiescent hepatic stellate cells (HSCs) into myofibroblasts. Mesenchyme homeobox 1 (MEOX1) is a transcription factors central to cellular development and differentiation. However, the role of MEOX1 signaling in hepatic fibrosis still remains largely unknown. In this study, we investigated the potential role and mechanism of MEOX1 in liver fibrosis using different models in vivo and in vitro. The hepatic expression of MEOX1 exhibited a positive correlation with the degree of fibrosis in patients diagnosed with non-alcoholic steatohepatitis (NASH), as determined through bioinformatics analysis. Furthermore, MEOX1 demonstrated high expression levels in activated HSCs and fibrotic liver tissues induced by methionine and choline-deficient diet (MCD), thioacetamide (TAA), or carbon tetrachloride (CCl₄) treatment in C57/BL6 mice. Mechanistically, MEOX1 facilitated HSC activation, proliferation, and migration. The comprehensive analysis of transcriptome sequencing and chromatin immunoprecipitation sequencing data revealed that connective tissue growth factor (CTGF) served as a target gene for MEOX1 in HSCs. Specifically, MEOX1 bound to the promoter region of CTGF and enhanced its transcriptional activity, thereby mediating the exacerbating effect of MEOX1 on hepatic fibrosis. In conclusion, our current findings elucidate the role of MEOX1 in exacerbating hepatic fibrosis progression through transcriptional activation of CTGF. Our findings provide valuable insights into the therapeutic potential of targeting MEOX1 for the treatment of hepatic fibrosis.