FOXS1 is increased in liver fibrosis and regulates TGFβ responsiveness and proliferation pathways in human hepatic stellate cells.

ABSTRACT: Liver fibrosis commences with liver injury stimulating transforming growth factor beta (TGFβ) activation of hepatic stellate cells (HSCs), causing scarring and irreversible damage. TGFβ induces expression of the transcription factor Forkhead box S1 (FOXS1) in hepatocytes and may have a role in the pathogenesis of hepatocellular carcinoma (HCC). To date, no studies have determined how it affects HSCs. We analyzed human livers with cirrhosis, HCC, and a murine fibrosis model and found that FOXS1 expression is significantly higher in fibrotic livers but not in HCC. Next, we treated human LX2 HSC cells with TGFβ to activate fibrotic pathways, and FOXS1 mRNA was significantly increased. To study TGFβ-FOXS1 signaling, we developed human LX2 FOXS1 CRISPR KO and scrambled control HSCs. To determin

SUBMITTER: Bates EA 

PROVIDER: S-EPMC10878791 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature