肝损伤
再灌注损伤
癌症研究
医学
炎症
下调和上调
气体6
免疫学
药理学
缺血
生物
受体
内科学
受体酪氨酸激酶
生物化学
基因
作者
Zhen Wang,Deng Liu,Qi Yan,Fang Liu,Mengting Zhan,Shunli Qi,Qi Fang,Ling Yao,Weizhi Wang,Ruixin Zhang,Jian Du,Lijian Chen
出处
期刊:Transplantation
[Ovid Technologies (Wolters Kluwer)]
日期:2022-05-11
卷期号:106 (7): 1351-1364
被引量:3
标识
DOI:10.1097/tp.0000000000004156
摘要
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.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.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.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.
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