A novel NEDD4L-TXNIP-CHOP axis in the pathogenesis of nonalcoholic steatohepatitis.

ABSTRACT: Background: Nonalcoholic steatohepatitis (NASH) is a leading cause of chronic liver diseases worldwide. There is a pressing clinical need to identify potential therapeutic targets for NASH treatment. Thioredoxin interacting protein (Txnip) is a stress responsive gene that has been implicated in the pathogenesis of NASH, but its exact role is not fully understood. Here, we investigated the liver- and gene-specific role of Txnip and its upstream/downstream signaling in the pathogenesis of NASH. Methods and Results: Using four independent NASH mouse models, we found that TXNIP protein abnormally accumulated in NASH mouse livers. A decrease in E3 ubiquitin ligase NEDD4L resulted in impaired TXNIP ubiquitination and its accumulation in the liver. TXNIP protein levels

SUBMITTER: Guo Q 

PROVIDER: S-EPMC10157740 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature