In this issue of <i>Science Signaling</i>, Sundaram <i>et al.</i> demonstrate a protective role for iRhom2 in promoting ADAM17-mediated shedding of TNFRs in hepatic stellate cells, which reduces TNFR signaling and liver fibrosis in response to injury.
Here, using the murine bile duct ligation (BDL) model, we showed that the abundance of iRhom2 and activation of ADAM17 increased during liver fibrosis.
These results indicate that ADAM17 mediates Ang II-induced EGFR transactivation on HSCs, and that this process may participate in the progression of liver fibrosis.
We showed an increased expression of the sheddases ADAM10 and ADAM17 in patients with chronic liver diseases that was associated with the severity of liver fibrosis.