Sorafenib attenuates liver fibrosis by triggering hepatic stellate cell ferroptosis via HIF-1α/SLC7A11 pathway.

ABSTRACT:

Objectives

Evidences demonstrate that sorafenib alleviates liver fibrosis via inhibiting HSC activation and ECM accumulation. The underlying mechanism remains unclear. Ferroptosis, a novel programmed cell death, regulates diverse physiological/pathological processes. In this study, we aim to investigate the functional role of HSC ferroptosis in the anti-fibrotic effect of sorafenib.

Materials and methods

The effects of sorafenib on HSC ferroptosis and ECM expression were assessed in mouse model of liver fibrosis induced by CCl₄ . In vitro, Fer-1 and DFO were used to block ferroptosis and then explored the anti-fibrotic effect of sorafenib by detecting α-SMA, COL1α1 and fibronectin proteins. Finally, HIF-1α siRNA, plasmid and stabilizers were applied to assess rela

SUBMITTER: Yuan S 

PROVIDER: S-EPMC8780895 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature