MicroRNA-146a Protects Against Ischemia/Reperfusion Liver Injury Through Inhibition of Toll-like Receptor 4 Signaling Pathway in Rats

Abstract

Hepatic ischemia/reperfusion injury (IRI) is a severe and common clinical challenge involved in liver surgery and transplantation. MicroRNA-146a (miR-146a) has recently been reported to be abnormally expressed in hepatic IRI, but the underlying mechanism is not fully elucidated. Accumulating evidences showed miR-146a targets Toll-like receptor 4 (TLR4) signaling pathway. Here, we found that miR-146a inhibited TLR4 signaling pathway accompanied by attenuated liver dysfunction, histologic injury and inflammation. Conversely, miR-146a inhibition increased TLR4 and interleukin-1 receptor-associated kinase, accompanied by exacerbated hepatic IRI and inflammation. Taken together, these data indicated that miR-146a protect against hepatic IRI via inhibiting TLR4 signaling pathway. In addition, we verified ultrasound microbubble-mediated gene transfection improved miR-146a transfection efficacy.