Increased CHCHD2 expression promotes liver fibrosis in nonalcoholic steatohepatitis via Notch/osteopontin signaling.

ABSTRACT: Nonalcoholic steatohepatitis (NASH) is closely related to liver fibrosis. The role of coiled-coil-helix-coiled-coil-helix domain-containing 2 (CHCHD2) in NASH remains unknown. CHCHD2's functions as a transcription factor have received much less attention than those in mitochondria. Herein, we systematically characterized the role of CHCHD2 as a transcription factor by chromatin immunoprecipitation sequencing and found its target genes were enriched in nonalcoholic fatty liver disease (NAFLD). Overall, CHCHD2 expression was found to be increased in the livers of patients with NAFLD and those of NASH mice. In line with these findings, CHCHD2 deficiency ameliorated NASH- and thioacetamide-induced liver fibrosis, whereas hepatocyte-specific CHCHD2 overexpression promoted liver fibrosis in NASH

SUBMITTER: Li Y 

PROVIDER: S-EPMC9746920 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature