Role of necroptosis in chronic hepatic inflammation and fibrosis in a mouse model of increased oxidative stress.

ABSTRACT: Mice deficient in the antioxidant enzyme Cu/Zn-superoxide dismutase (Sod1^-/- or Sod1KO mice) have increased oxidative stress, show accelerated aging and develop spontaneous hepatocellular carcinoma (HCC) with age. Similar to humans, HCC development in Sod1KO mice progresses from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) with fibrosis, which eventually progresses to HCC. Oxidative stress plays a role in NAFLD to NASH progression, and liver inflammation is the main mechanism that drives the disease progression from NASH to fibrosis. Because necroptosis is a major source of inflammation, we tested the hypothesis that increased necroptosis in the liver plays a role in increased inflammation and fibrosis in Sod1KO mice. Phosphorylation of MLKL

SUBMITTER: Mohammed S 

PROVIDER: S-EPMC8845573 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature