Context-dependent contribution of peptidyl arginine deiminase 4 (PAD4) to neutrophil extracellular trap formation and liver injury in acute and chronic hepatotoxicant challenge.

ABSTRACT: Neutrophils play a complex role in the pathogenesis of chronic liver disease and have been linked to both liver damage and injury resolution. Recent reports propose that neutrophils drive liver injury and fibrosis through the formation of neutrophil extracellular traps (NETs). This study tests the hypothesis that the enzyme peptidyl arginine deiminase-4 (PAD4) drives NET formation and liver fibrosis in experimental chronic liver injury. Wild-type (PAD4+/+) and PAD4-deficient (PAD4-/-) mice were chronically challenged twice weekly with carbon tetrachloride (CCl4, 1 ml/kg, i.p) or vehicle (corn oil) for 6 weeks, and samples were collected 24 h after the final challenge. In separate studies, mice were challenged once, and samples were collected 24 to 48 h later. Circulating NET biomarkers (e.

SUBMITTER: Capece GE 

PROVIDER: S-EPMC12599872 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature