β-Arrestin-2 attenuates hepatic ischemia-reperfusion injury by activating PI3K/Akt signaling
| Autor: | Zhi-ying Feng, Li Wang, Wu Bin, Guihua Chen, Hai Jin, Long Xia, Zhou Jing, Xiaolong Chen, JianXu Yang, Yang Yang, Hui Li, Junbin Zhang, Huilin Liu, Zhang Lei, Gen-shu Wang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Aging
Apoptosis Pharmacology Protective Agents Pathogenesis hepatic surgery Mice Phosphatidylinositol 3-Kinases Liver Function Tests PI3K/Akt signaling pathway medicine Animals RNA Small Interfering Receptor Protein kinase B hepatic ischemia-reperfusion injury PI3K/AKT/mTOR pathway Liver injury Gene knockdown liver transplantation business.industry Liver Diseases Cell Biology medicine.disease beta-Arrestin 2 Mice Inbred C57BL β-Arrestin-2 Gene Knockdown Techniques Reperfusion Injury Hepatocytes business Reperfusion injury Proto-Oncogene Proteins c-akt Research Paper Signal Transduction |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|