Research Paper Volume 13, Issue 2 pp 2251—2263
β-Arrestin-2 attenuates hepatic ischemia-reperfusion injury by activating PI3K/Akt signaling
- 1 Department of Hepatic Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, P. R. China
- 2 Guangdong Provincial Key Laboratory of Liver Disease Research, Guangzhou 510630, Guangdong Province, P. R. China
- 3 Department of Gastroenterology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, P. R. China
- 4 Department of Pathology, The Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, P. R. China
- 5 Department of Medical Ultrasonics, Guangzhou First People’s Hospital, The Second Affiliated Hospital of South China University of Technology, Guangzhou 510630, Guangdong Province, P. R. China
- 6 Department of Intensive Care Unit, Henan Provincial People's Hospital, Zhengzhou 450003, Henan Province, P. R. China
- 7 Department of Biliary-Pancreatic Surgery, The Third Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510630, Guangdong Province, P. R. China
Received: January 28, 2020 Accepted: September 24, 2020 Published: December 11, 2020
https://doi.org/10.18632/aging.202246How to Cite
Copyright: © 2020 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Hepatic ischemia-reperfusion injury (IRI) remains a common complication during liver transplantation (LT), partial hepatectomy and hemorrhagic shock in patients. As a member of the G protein-coupled receptors adaptors, ARRB2 has been reported to be involved in a variety of physiological and pathological processes. However, whether β-arrestin-2 affects the pathogenesis of hepatic IRI remains unknown. The goal of the present study was to determine whether ARRB2 protects against hepatic IR injury and elucidate the underlying mechanisms. To this end, 70% hepatic IR models were established in ARRB2 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.