Protecting against liver fibrosis

Fibrosis Chronic liver disease stimulates hepatic stellate cells and ultimately leads to fibrosis. Sundaram et al. found that mice lacking the pseudoprotease iRhom2, which activates the metalloprotease ADAM17, showed increased stellate cell activation and susceptibility to liver fibrosis induced by bile duct ligation (see the Focus by Badenes and Adrain). iRhom2-activated ADAM17 promoted the shedding of tumor necrosis factor (TNF) receptors from stellate cells. Treating iRhom2-deficient mice with the TNF-α inhibitor etanercept reduced liver fibrosis induced by bile duct ligation. Sci. Signal. 12 , eaax1194, eaaz0444 (2019).