E2F2 Reprograms Macrophage Function By Modulating Material and Energy Metabolism in the Progression of Metabolic Dysfunction-Associated Steatohepatitis.

ABSTRACT: Macrophages are essential for the development of steatosis, hepatic inflammation, and fibrosis in metabolic dysfunction-associated steatohepatitis(MASH). However, the roles of macrophage E2F2 in the progression of MASH have not been elucidated. This study reveals that the expression of macrophage E2F2 is dramatically downregulated in MASH livers from mice and humans, and that this expression is adversely correlated with the severity of the disease. Myeloid-specific E2F2 depletion aggravates intrahepatic inflammation, hepatic stellate cell activation, and hepatocyte lipid accumulation during MASH progression. Mechanistically, E2F2 can inhibit the SLC7A5 transcription directly. E2F2 deficiency upregulates the expression of SLC7A5 to mediate amino acids flux, resulting in enhanced glycolysis,

SUBMITTER: Liu Z 

PROVIDER: S-EPMC11672278 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature