Gasdermin-E-Dependent Non-Canonical Pyroptosis Promotes Drug-Induced Liver Failure by Promoting CPS1 deISGylation and Degradation.

ABSTRACT: Drug-induced liver injury (DILI) is a significant global health issue that poses high mortality and morbidity risks. One commonly observed cause of DILI is acetaminophen (APAP) overdose. GSDME is an effector protein that induces non-canonical pyroptosis. In this study, the activation of GSDME, but not GSDMD, in the liver tissue of mice and patients with APAP-DILI is reported. Knockout of GSDME, rather than GSDMD, in mice protected them from APAP-DILI. Mice with hepatocyte-specific rescue of GSDME reproduced APAP-induced liver injury. Furthermore, alterations in the immune cell pools observed in APAP-induced DILI, such as the replacement of TIM4⁺ resident Kupffer cells (KCs) by monocyte-derived KCs, Ly6C⁺ monocyte infiltration, MerTk⁺ macrophages depletion,

SUBMITTER: Ouyang SX 

PROVIDER: S-EPMC11040357 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature