TEAD4-mediated upregulation of LPAR3 augments hepatic stellate cell activation in portal hypertension.

ABSTRACT: Based on bioinformatics insights, this study investigates the functions of lysophosphatidic acid receptor 3 (LPAR3) and TEA domain transcription factor 4 (TEAD4) in hepatic stellate cell (HSC) activation and portal hypertension (PHT) progression. LPAR3 exhibited heightened expression in transforming growth factor beta 1-activated human HSCs (LX-2) and in the liver of carbon tetrachloride-challenged mice. Knockdown of LPAR3 alleviated activation and contractile activity of LX-2 cells, as well as ameliorated liver injury and fibrosis in PHT mice, achieved through deactivation of the p38 MAPK and PI3K/AKT signaling. TEAD4, which was enhanced in the activated LX-2 cells and the liver of PHT mice, was identified to bind to the promoter of LPAR3 to promote its transcription. Silencing of TEAD4 s

SUBMITTER: Qi R 

PROVIDER: S-EPMC12214033 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature