RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway

作     者：Yongsheng Tang Zenan Yuan Xu Lu Yingqiu Song Shuguang Zhu Chunhui Qiu Qi zhang Binsheng Fu Changchang Jia Hua Li 

作者机构：Department of Hepatic SurgeryLiver Transplantation CenterThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Gastrointestinal SurgeryThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina Department of Cell-Gene Therapy Translational Medicine Research CenterThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina 

出 版 物：《Journal of Clinical and Translational Hepatology》 (临床与转化肝病杂志（英文版）)

年 卷 期：2024年第12卷第4期

页      面：357-370页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by:The National Natural Science Foundation of China(82270688,81402426) The Natural Science Foundation.of Guangdong Province(2021A1515010726,2022A1515012650,2020A1515010302) The Cultivation Project of National Natural Science Foundationof the Third Affliated Hospital of Sun Yat-sen University(No.2020GzRPYMS09) Science and Technology ProjectsinGuangzhou(No.202102010310,202201020427) 

主　　题：Hepatic ischemia-reperfusion injury(HIRI) Receptor activity-modifying protein 1(RAMP1) YES-Associated Protein(YAP) Extracellular signalregulated kinase(ERK) 

摘      要：Background and Aims:Hepatic ischemia-reperfusion injury(HIRI)is a prevalent complication of liver transplantation,partial hepatectomy,and severe infection,necessitating the development of more effective clinical *** activity–modifying protein 1(RAMP1),a member of the G protein–coupled receptor adapter family,has been implicated in numerous physiological and pathological *** study aimed to investigate the pathogenesis of RAMP1 in ***:We established a 70%liver ischemia-reperfusion model in RAMP1 knockout(KO)and wild-type *** and blood samples were collected after 0,6,and 24 h of hypoxia/*** histological and serological analyses were performed to evaluate liver *** also conducted in-vitro and in-vivo experiments to explore the molecular mechanism underlying RAMP1 ***:Liver injury was exacerbated in RAMP1-KO mice compared with the sham group,as evidenced by increased cell death and elevated serum transaminase and inflammation *** was promoted in RAMP1-KO mice via the induction of hepatocyte apoptosis and inhibition of *** absence of RAMP1 led to increased activation of the extracellular signal–regulated kinase(ERK)/mitogen-activated protein kinase(MAPK)pathway and yes-associated protein(YAP)phosphorylation,ultimately promoting ***772984,an ERK/MAPK phosphorylation inhibitor,and PY-60,a YAP phosphorylation inhibitor,reduced apoptosis in in-vitro and in-vivo ***:Our findings suggest that RAMP1 protects against HIRI by inhibiting ERK and YAP phosphorylation signal transduction,highlighting its potential as a therapeutic target for HIRI and providing a new avenue for intervention.