MicroRNA‐449b‐5p targets HMGB1 to attenuate hepatocyte injury in liver ischemia and reperfusion

Abstract MicroRNAs (miRNAs) participate in the pathological process of liver ischemia/reperfusion (I/R) injury. MiR‐449b‐5p is the target miRNA of high mobility group box 1 (HMGB1). Its role and molecular mechanism in liver I/R injury remain unidentified. In this study, we found a protective effect of miR‐449b‐5p against hepatic I/R injury. HMGB1 expression significantly increased, whereas miR‐449b‐5p dramatically decreased in patients after liver transplant and in L02 cells exposed to hypoxia/reoxygenation (H/R). A dual‐luciferase reporter assay confirmed the direct interaction between miR‐449b‐5p and the 3′ untranslated region of HMGB1 messenger RNA. We also found that overexpression of miR‐449b‐5p significantly promoted cell viability and inhibited cell apoptosis of L02 cells exposed to H/R. Moreover, miR‐449b‐5p repressed HMGB1 protein expression and nuclear factor‐κB (NF‐κB) pathway activation in these L02 cells. In an in vivo rat model of hepatic I/R injury, overexpression of miR‐449b‐5p significantly decreased alanine aminotransferase and aspartate aminotransferase and inhibited the HMGB1/NF‐κB pathway. Our study thus suggests that miR‐449b‐5p alleviated hepatic I/R injury by targeting HMGB1 and deactivating the NF‐κB pathway, which may provide a novel and promising therapeutic target for hepatic I/R injury.