MiR150‐knockout prevents Fas‐induced liver injury via Akt pathway

Abstract

MicroRNA 150 has been reported to involve in a diversity of cellular process such as hematopoiesis, cell differentiation, proliferation, and apoptosis. However, its potential implication in liver injury has not been investigated. In this study, we use miR150 knockout (KO) and wild type (WT) mouse models to investigate the effect of miR150 in Fas‐induced hepatocyte apoptosis and liver injury in vivo. The wild type (WT) mice and miR150 knockout (KO) mice were treated with anti‐Fas antibody Jo2 (0.5μg/g of body weight) for 2 to 4 hours, and the extent of liver injury was assessed by histopathology, serum aminotransferases, TUNEL staining, and caspase activation. The miR150 KO mice showed resistant to Fas‐induced liver injury in comparison to WT mice; this was reflected by the lower alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, less liver damage, and less hepatocyte apoptosis (P<0.01). After Jo2 treatment, the protein and phosphorylation levels of AKT (the bona fide predict target of miR150) significantly decreased in WT mice but not in miR150 KO mice. Pretreatment with Akt inhibitor V (an Akt inhibitor) exacerbated Jo2‐mediated liver injury in miR150 KO mice. Furthermore, at lower Fas agonist dose (0.35μg/g of body weight), miR150 KO mice developed mild liver injury and all the treated mice survived, whereas WT mice showed severe liver injury and died within 10 hours. Taken together, these findings demonstrate that miR150 deficient prevents Fas‐induced hepatocyte apoptosis and liver injury and this protection is partly mediated by Akt‐induced signaling transduction pathway.