Redundant Functions of ERK1 and ERK2 Maintain Mouse Liver Homeostasis Through Down-Regulation of Bile Acid Synthesis.

ABSTRACT: Activation of extracellular signal-regulated kinase (ERK) 1/2 promotes hepatocyte proliferation in response to growth stimuli, but whether constitutive hepatocyte ERK1/2 signaling functions in liver physiology is unknown. To examine the role of ERK1/2 in hepatic homeostasis, the effects of a knockout of Erk1 and/or Erk2 in mouse liver were examined. The livers of mice with a global Erk1 knockout or a tamoxifen-inducible, hepatocyte-specific Erk2 knockout were normal. In contrast, Erk1/2 double-knockout mice developed hepatomegaly and hepatitis by serum transaminases, histology, terminal deoxynucleotide transferase-mediated deoxyuridine triphosphate nick end-labeling, and assays of hepatic inflammation. Liver injury was associated with biochemical evidence of cholestasis with increased seru

SUBMITTER: Cingolani F 

PROVIDER: S-EPMC9035584 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature