Activated AXL Protects Against Hepatic Ischemia-reperfusion Injury by Upregulating SOCS-1 Expression. Issue 7 (11th May 2022)

• Record Type: Journal Article
• Authors: Wang, Zhen; Liu, Deng; Yan, Qi; Liu, Fang; Zhan, Mengting; Qi, Shunli; Fang, Qi; Yao, Lei; Wang, Weizhi; Zhang, Ruixin; Du, Jian; Chen, Lijian
• Is Part Of: Transplantation. Volume 106:Issue 7(2022)
• Page Start: 1351
• Page End: 1364
• Publication Date: 2022-05-11
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000004156
• Languages: English
• ISSNs: 0041-1337

Abstract

Abstract : Background: Hepatic ischemia-reperfusion (I/R) injury is the main factor affecting the morbidity and mortality associated with perioperative complications of liver transplantation and major hepatectomy. AXL is a member of the TYRO3, AXL, MERTK family and is involved in immune and apoptosis processes in multiple organs. However, the role of AXL in hepatic I/R injury remains to be elucidated. Methods: Mice pretreated with rmGas6 or R428 and mice tail vein injected with adeno-associated virus knockdown suppressor of cytokine signaling protein-1 (SOCS-1) underwent liver I/R surgery to detect the function of activated AXL in vivo. Primary hepatocytes undergo hypoxic reoxygenation injury in vitro. Results: AXL expression was significantly upregulated, and phosphorylated-AXL was substantially downregulated in liver transplantation patients and hepatic I/R surgery mice. A mouse model of hepatic I/R injury showed that AXL activation reduced liver inflammation and liver cells apoptosis. The inhibition of AXL activation (AXL-specific inhibitor R428) aggravated hepatic I/R injury, resulted in larger areas of liver injury, aggravated inflammatory response, and increased apoptosis of liver cells. In addition, activated AXL promotes the expression level of SOCS-1 and inhibits toll-like receptor 4 and its downstream signaling pathways. Finally, SOCS-1 was knocked down with an adeno-associated virus, and activated AXL failed to protect against hepatic I/R injury. Conclusions: AXL activation protects the liver from I/R injury by upregulating SOCS-1 and inhibiting the toll-like receptor 4/myeloid differentiation factor-88/nuclear factor kappa-B signaling axis. Targeting AXL may be a new therapeutic option for ameliorating hepatic I/R injury.