Role of HNF4alpha-cMyc Interaction in CDE-diet Induced Liver Injury and Regeneration

This study investigated the role of HNF4α-cMyc interaction in regulating liver injury and regeneration using the choline-deficient and ethionine-supplemented (CDE) diet model. WT, hepatocyte-specific HNF4α-KO, cMyc-KO, and HNF4α-cMyc double knockout (DKO) mice were fed a CDE diet for one week to induce subacute liver injury. To study regeneration, CDE diet was followed by normal chow diet for one week. WT mice showed significant liver injury and decreased HNF4α mRNA and protein expression after one week of a CDE diet. HNF4α deletion resulted in significantly higher injury with increased inflammation, fibrosis, proliferation, and HPC activation compared to WT mice after CDE diet feeding but similar recovery. Deletion of cMyc substantially lowered liver injury with activation of inflammatory genes activation compared to WT and HNF4α-KO mice after CDE diet feeding. DKO mice resulted in phenotype comparable to the HNF4α-KO mice after CDE diet feeding and led to complete recovery. DKO mice showed a significant increase in HPC markers both following CDE-induced injury and after one week of recovery. Taken together, these data show that HNF4α protects against inflammatory and fibrotic change following CDE diet-induced injury, which is driven by cMyc.PMID:38588852 | DOI:10.1016/j.ajpath.2024.03.008
Source: The American Journal of Pathology - Category: Pathology Authors: Source Type: research