MiR-451a ameliorates alcoholic hepatitis via repressing HDAC8-mediated proinflammatory response

Abstract

Alcoholic hepatitis (AH) is identified as an inflammatory syndrome with high morbidity and mortality as a result of severe hepatocellular dysfunction and liver injury. Accumulated studies indicated that miRNAs are involved in AH. The potential effect of miR-451a in AH mice was examined in the current study. A mice AH model was established and the miR-451a expression in AH mice compared with the sham group was tested by real-time polymerase chain reaction (qRT-PCR). AH mice were injected with pre-miR-451a lentivirus for miR-451a overexpression and histone deacetylase (HDAC8) lentivirus for HDAC8 overexpression in AH mice. The underlying mechanisms were explored by searching the potential target genes of miR-451a in miRanda database and then we confirmed this. We found that miR-451a expression was significantly decreased in AH mice compared with the sham group. Moreover, miR-451a overexpression alleviated alcohol-induced liver inflammation and injuries of AH mice. Additionally, further mechanism exploration disclosed that HDAC8 was a target of miR-451a. The protective effect of miR-451a on AH in AH mice was abolished by HDAC8 overexpression. In summary, miR-451a ameliorates AH via repressing HDAC8-mediated proinflammatory response.

Keywords: HDAC8; alcoholic hepatitis; inflammation; miR-451a.