Let-7 suppresses liver fibrosis by inhibiting hepatocyte apoptosis and TGF-β production.

ABSTRACT:

Objective

FAS-mediated apoptosis of hepatocytes and aberrant TGF-β signaling are major drivers of liver fibrosis. Decreased miRNA let-7 expression in the livers of patients and animals with fibrosis suggests a mechanistic link of let-7 to hepatic fibrogenesis.

Methods

Using transient transfection we tested the effects of let-7 overexpression and TET3 siRNA knockdown on FAS and TGF-β1 expression and FAS-mediated apoptosis in human and mouse primary hepatocytes. We assessed the therapeutic activity of let-7 miRNA delivered via adeno-associated viral vectors in mouse models of carbon tetrachloride (CCl₄)-induced and bile duct ligation (BDL)-induced liver fibrosis.

Results

Let-7 decreased TGF-β1 production from hepatocytes through a negative feedback loop invol

SUBMITTER: Song J 

PROVIDER: S-EPMC10641683 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature