Cyr61 Alleviates Cholangitis by Inhibiting Cytotoxic Effects of CD8^(+) T Cells on Biliary Epithelial Cells  

作　　者：Tiao-chun CHENG Han LI Xi LUO Lin-ling JU Lin CHEN Jian-guo SHAO Yong-jun SHE Min LI Zhao-lian BIAN 

机构地区：[1]Medical School of Nantong University,Nantong 226006,China [2]Nantong Institute of Liver Disease,Nantong Third People’s Hospital Nantong University,Nantong 226006,China [3]Department of Gastroenterology and Hepatology,Nantong Third People’s Hospital,Nantong University,Nantong 226006,China [4]Department of Anesthesiology,Nantong Third People’s Hospital,Nantong University,Nantong 226006,China

出　　处：《Current Medical Science》2021年第6期1205-1213,共9页当代医学科学（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(No.81600449);the Nantong Science and Technology Bureau(No.MS22018007 and No.MSZ18130);Six Peak Talents in Jiangsu Province(No.YY-177);the Project of Jiangsu Province Youth Medical Talent Development(No.QNRC2016400);the Project of Nantong Youth Medical Talent Development(No.05).

摘　　要：Objective:Primary biliary cholangitis(PBC)is a chronic progressive cholestatic liver disease.In recent years,researchers have found that cysteine-rich angiogenic inducer 61(Cyr61,also known as CCN1)has a potential role in reducing portal inflammation in patients with PBC.This study aimed to explore the relationship between Cyr61 and PBC to provide new ideas and an experimental basis for the clinical treatment of PBC.Methods:After induction of the overexpression of Cyr61 in a mouse model of PBC using recombinant adenovirus,hematoxylin and eosin staining and pathological scores were used to indicate intrahepatic inflammation and bile duct damage.Real-time PCR was used to detect changes in inflammation-related cytokines in the liver.To further study the mechanism,we assessed whether Cyr61 protects bile duct epithelial cells from cytotoxic effects.Results:Serum and hepatic Cyr61 levels were increased in the murine model of PBC.Overexpression of Cyr61 alleviated hepatic inflammation and bile duct injury in vivo.Cyr61 inhibited the cytotoxic effects of CD8^(+)T cells by acting on biliary epithelial cells(BECs)in vitro.Conclusion:Our results provide novel insight into the pathogenesis of PBC and suggest that Cyr61 plays a dominant role in the cytotoxic effects on BECs in PBC.Consequently,therapeutic strategies targeting Cyr61 could be a potent therapy for PBC.

关 键 词：cysteine-rich angiogenic inducer 61 primary biliary cholangitis inflammation bile duct damage CYTOTOXICITY 

分 类 号：R73[医药卫生—肿瘤]