TM4SF5-mediated KEAP1 Regulation in Hepatocytes Irrelevant to NRF2 Expression and Activity Promotes Oxidative Stress and Inflammation to Develop Metabolic Dysfunction-Associated Steatotic Liver Disease.

ABSTRACT: Metabolic dysfunction-associated steatohepatitis (MASH)-associated fibrosis involves inflammation accompanied by reactive oxygen species (ROS), in addition to abnormal lipid metabolism and extracellular matrix (ECM) deposition. ROS levels are regulated by the NRF2-KEAP1 pathway. Transmembrane 4 L six family member 5 (TM4SF5) is implicated in metabolic dysfunction-associated steatotic liver disease (MASLD). However, it remains unknown how hepatocyte TM4SF5 modulates abnormal lipid and ROS accumulations during MASLD development. Here we assessed the influence of TM4SF5 on NRF2-KEAP1 pathway utilizing various in vitro and in vivo MASLD models. Our results indicate that hepatocyte TM4SF5 downregulates KEAP1 in physiological states and stabilizes KEAP1 in pathological conditions,

SUBMITTER: Shin EA 

PROVIDER: S-EPMC12836525 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature