Moderate, chronic ethanol feeding exacerbates carbon-tetrachloride-induced hepatic fibrosis via hepatocyte-specific hypoxia inducible factor 1α

ABSTRACT: The hypoxia-sensing transcriptional factor HIF1α is implicated in a variety of hepato-pathological conditions; however, the contribution of hepatocyte-derived HIF1α during progression of alcoholic liver injury is still controversial. HIF1α induces a variety of genes including those involved in apoptosis via p53 activation. Increased hepatocyte apoptosis is critical for progression of liver inflammation, stellate cell activation and fibrosis. Using hepatocyte-specific HIF1α-deficient mice (ΔHepHIF1α-/-), here we investigated the contribution of HIF1α to ethanol-induced hepatocyte apoptosis and its role in amplification of fibrosis after carbon tetrachloride (CCl₄) exposure. Moderate ethanol feeding (11% of Kcal) induced accumulation of hypoxia-sensitive pimonidazole adducts and H

SUBMITTER: Roychowdhury S 

PROVIDER: S-EPMC4115456 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature