IRhom2 regulates HMGB1 secretion to modulate inflammation and hepatocyte senescence in an in vitro model of ischemia-reperfusion injury.

ABSTRACT: Ischemia-reperfusion injury (IRI) represents a major challenge in liver transplantation, driving acute dysfunction and contributing to long-term allograft rejection. This process triggers a robust inflammatory response, leading to hepatocyte damage, senescence, and impaired liver regeneration. While the underlying mechanisms remain incompletely understood, increasing evidence highlights macrophage-derived signaling as a pivotal driver of hepatocyte fate during IRI. Here, we identify iRhom2 as a key regulator of immune-mediated liver injury, orchestrating macrophage-driven inflammation and hepatocyte senescence. iRhom2 is known to modulate the secretion of multiple cytokines by macrophages, yet its specific contribution to IRI-driven hepatocyte senescence has not been fully elucidated. We r

SUBMITTER: Calligaris M 

PROVIDER: S-EPMC12780076 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature