HAF prevents hepatocyte apoptosis and progression to MASH and HCC through transcriptional regulation of the NF-κB pathway.

ABSTRACT:

Background and aims

HCC incidence is increasing worldwide due to the obesity epidemic, which drives metabolic dysfunction-associated steatohepatitis (MASH) that can lead to HCC. However, the molecular pathways driving MASH-HCC are poorly understood. We have previously reported that male mice with haploinsufficiency of hypoxia-associated factor (HAF) ( SART1+/ - ) spontaneously develop MASH-HCC. However, the cell type(s) responsible for HCC associated with HAF loss are unclear.

Approach and results

We generated SART1 -floxed mice, which were crossed with mice expressing Cre recombinase within hepatocytes (Alb-Cre; hepS -/- ) or myeloid cells (LysM-Cre, macS -/- ). HepS - / - mice (both male and female) developed HCC associated with profound inflammatory and lipid dysregulatio

SUBMITTER: Acuna-Pilarte K 

PROVIDER: S-EPMC12266801 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature