In-vitro validation of potential modulators of non-alcoholic fatty liver disease (NAFLD)

Abstract

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver injury, compromising the liver’s regenerative ability and promoting fibrosis. Despite its widespread impact, therapeutic options remain limited. The only FDA-approved drug for NASH, Rezdiffra, had limited efficacy in patients, highlighting the need for alternative strategies. This study aims to identify genes that enhance hepatocyte survival and regeneration in NAFLD. Our preliminary functional genetic screen, utilizing 500 shRNAs, has suggested several enriched candidates potentially involved in the development and progression of NAFLD. Targeting these genes through shRNA-mediated downregulation holds the potential to enhance liver proliferation. Two promising candidates, Target01 and Target02, were selected for in vitro validation via cell migrative and proliferative assays. Our data revealed that the knockdown of Target02 increased the migrative capacity of hepatocytes. On the other hand, the downregulation of Target01 had no significant effect on cell proliferation and migration. These findings suggest that Target02 may offer a therapeutic pathway to improve liver regeneration in NAFLD, though further assays are necessary to confirm its potential.