Lin28A Drives hepatic fibrosis by suppressing HMGA2/HIF-1α-Dependent ferroptosis in hepatic stellate cells - PubMed
3 hours ago
- #Liver Fibrosis
- #Lin28A
- #Ferroptosis
- Lin28A is upregulated in human cirrhotic and mouse fibrotic livers, particularly in hepatic stellate cells (HSCs).
- HSCs-specific overexpression of Lin28A worsened carbon tetrachloride (CCl4)-induced fibrosis in mice.
- Lin28A knockdown in HSCs suppressed activation and induced ferroptosis markers like mitochondrial damage and lipid peroxidation.
- Lin28A represses let-7 microRNAs, increasing HMGA2 expression, which alongside HIF-1α downregulates ferroptosis defense proteins SLC7A11 and GPX4.
- The Lin28A inhibitor C1632 showed anti-fibrotic effects by inducing ferroptosis, reversible by ferrostatin-1.
- C1632 treatment alleviated CCl4-induced liver fibrosis in vivo, suggesting Lin28A as a potential therapeutic target.