Ferroptosis regulatory axis in activated hepatic stellate cells

The ferroptosis regulatory axis in activated hepatic stellate cells (HSCs) is a biological pathway that mediates iron-dependent, oxidative cell death in the primary drivers of liver fibrosis (Source: PubMed, PMID: 33553101). Activated HSCs transition from vitamin A-storing cells to myofibroblast-like cells that secrete excessive collagen; inducing ferroptosis in these specific cells is a promising strategy to resolve fibrosis and prevent progression to cirrhosis (Source: NIH, National Institute of Diabetes and Digestive and Kidney Diseases). This axis is primarily controlled by the System Xc-/Glutathione/GPX4 antioxidant system, which prevents the lethal accumulation of lipid hydroperoxides (Source: Nature, Cell Death & Disease, 2021). Drugs such as Erastin, Sorafenib, and RSL3 can trigger this axis by inhibiting these protective mechanisms or by increasing the intracellular labile iron pool, leading to targeted HSC clearance (Source: Frontiers in Pharmacology, 2022). While therapeutically potent, the main challenge lies in achieving cell-type specificity to avoid off-target ferroptosis in healthy hepatocytes or other vital tissues (Source: Journal of Hepatology, 2021).

Other names

HSC ferroptosis pathwayFerroptosis-mediated HSC inactivationHepatic stellate cell ferroptosis signalingFerroptosis in liver fibrosis

Induction of iron-dependent programmed cell death (ferroptosis) through the inhibition of the System Xc-/GPX4 antioxidant axis or the promotion of iron accumulation and lipid peroxidation specifically within activated hepatic stellate cells.