Gasdermin D deletion prevents liver injury and exacerbates extrahepatic damage in a murine model of alcohol-induced ACLF.

ABSTRACT:

Background

Gasdermin D (GSDM-D), a key executor of pyroptosis, is increased in various liver diseases and contributes to disease progression. Alcohol induces inflammasome activation and cell death, which are both linked to GSDM-D activation. However, its role in alcohol-induced acute-on-chronic liver failure (ACLF) remains unclear.

Methods

ACLF was induced in GSDM-D-deficient or wild-type (WT) mice by 28-day bile duct ligation surgery plus a single 5 g/kg alcohol binge leading to acute decompensation. Nine hours after the alcohol binge, blood, liver, kidney and cerebellum specimens were collected for analysis.

Results

Active GSDM-D was significantly increased in humans and mice ACLF livers compared with both healthy controls and cirrhotic livers. GSDM-D-deficient mice

SUBMITTER: Ortega-Ribera M 

PROVIDER: S-EPMC11934631 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature