β-Arrestin-2 attenuates hepatic ischemia-reperfusion injury by activating PI3K/Akt signaling
Xiaolong Chen, Junbin Zhang, Long Xia, Li Wang, Hui Li, Huilin Liu, Jing Zhou, Zhiying Feng, Hai Jin, Jianxu Yang, Yang Yang, Bin Wu, Lei Zhang, Guihua Chen, Genshu Wang
Abstract
knockdown mice and wild-type littermates, with blood and liver samples collected at 1, 6 and 12 h after reperfusion to evaluate liver injury. The effect of ARBB2 on PI3K/Akt signaling during IR injury was evaluated in vivo, and PI3K/Akt pathway regulation by ARRB2 was further assessed in vitro. Our results showed that ARRB2 knockdown aggravates hepatic IR injury by promoting the apoptosis of hepatocytes and inhibiting their proliferation. In addition, ARRB2 deficiency inhibited PI3K/Akt pathway activation, while the administration of the PI3K/Akt inhibitor PX866 resulted in severe IR injury in mice. Furthermore, the liver-protecting effect of ARRB2 was shown to depend on PI3K/Akt pathway activation. In summary, our results suggest that β-Arrestin-2 protects against hepatic IRI by activating PI3K/Akt signaling, which may provide a novel therapeutic strategy for treating liver ischemia-reperfusion injury.