Angiotensin Ⅱ type-2 receptor signaling facilitates liver injury repair and regeneration via inactivation of Hippo pathway  

作　　者：Chang-yong Xu Ji Jiang Yue An Peng-fei Ye Cun-cun Zhang Ning-ning Sun Sai-nan Miao Meng-qi Chai Wen-min Liu Mei Yang Wei-hua Zhu Jing-jing Yu Man-man Yu Wu-yi Sun Huan Qiu Shi-hao Zhang Wei Wei 

机构地区：[1]Institute of Clinical Pharmacology,Anhui Medical University/Key Laboratory of Anti-Inflammatory and Immune Medicine,Ministry of Education,Anhui Collaborative Innovation Centre of Anti-Inflammatory and Immune Medicine,Hefei,230032,China [2]School of Nursing,Anhui Medical University,Hefei,230032,China

出　　处：《Acta Pharmacologica Sinica》2024年第6期1201-1213,共13页中国药理学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(81871973 to SHZ);the Basic and Clinical Cooperative Research and Promotion Program of Anhui Medical University(2020xkjT023 to HQ).

摘　　要：The angiotensin Ⅱ type 2 receptor(AT2R)is a well-established component of the renin-angiotensin system and is known to counteract classical activation of this system and protect against organ damage.Pharmacological activation of the AT2R has significant therapeutic benefits,including vasodilation,natriuresis,anti-inflammatory activity,and improved insulin sensitivity.However,the precise biological functions of the AT2R in maintaining homeostasis in liver tissue remain largely unexplored.In this study,we found that the AT2R facilitates liver repair and regeneration following acute injury by deactivating Hippo signaling and that interleukin-6 transcriptionally upregulates expression of the AT2R in hepatocytes through STAT3 acting as a transcription activator binding to promoter regions of the AT2R.Subsequently,elevated AT2R levels activate downstream signaling via heterotrimeric G protein Gα12/13-coupled signals to induce Yap activity,thereby contributing to repair and regeneration processes in the liver.Conversely,a deficiency in the AT2R attenuates regeneration of the liver while increasing susceptibility to acetaminophen-induced liver injury.Administration of an AT2R agonist significantly enhances the repair and regeneration capacity of injured liver tissue.Our findings suggest that the AT2R acts as an upstream regulator in the Hippo pathway and is a potential target in the treatment of liver damage.

关 键 词：angiotensinⅡtype 2 receptor liver injury liver regeneration Hippo pathway Yap 

分 类 号：R575[医药卫生—消化系统]