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Article Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation

文献类型：期刊论文

作者Zhu, Weize8; Hong, Ying8; Tong, Zhaowei7; He, Xiaofang8; Li, Yan8; Wang, Hao8; Gao, Xinxin8; Song, Pengtao6; Zhang, Xianshan7; Wu, Xiaochang1
刊名CELL REPORTS MEDICINE
出版日期2024-03-19
卷号5期号:3页码:25
ISSN号2666-3791
DOI10.1016/j.xcrm.2024.101477
通讯作者Hong, Ying(Zhongjing1003@126.com) ; He, Xiaofang(llsheng@shutcm.edu.cn) ; Li, Yan(mingxiaoli0928@126.com) ; Li, Mingxiao(mingxiaoli0928@126.com) ; Zhong, Jing(Zhongjing1003@126.com) ; Sheng, Lili(llsheng@shutcm.edu.cn) ; Li, Houkai(mingxiaoli0928@126.com)
英文摘要Metabolic (dysfunction) -associated steatohepatitis (MASH) is the advanced stage of metabolic (dysfunction) -associated fatty liver disease (MAFLD) lacking approved clinical drugs. Adenosine A1 receptor (A 1 R), belonging to the G -protein -coupled receptors (GPCRs) superfamily, is mainly distributed in the central nervous system and major peripheral organs with wide-ranging physiological functions; however, the exact role of hepatic A 1 R in MAFLD remains unclear. Here, we report that liver -specific depletion of A 1 R aggravates while overexpression attenuates diet -induced metabolic -associated fatty liver (MAFL)/ MASH in mice. Mechanistically, activation of hepatic A 1 R promotes the competitive binding of sterol -regulatory element binding protein (SREBP) cleavage -activating protein (SCAP) to sequestosome 1 (SQSTM1), rather than protein kinase A (PKA) leading to SCAP degradation in lysosomes. Reduced SCAP hinders SREBP1c/2 maturation and thus suppresses de novo lipogenesis and inflammation. Higher hepatic A 1 R expression is observed in patients with MAFL/MASH and high -fat diet (HFD)-fed mice, which is supposed to be a physiologically adaptive response because A 1 R agonists attenuate MAFL/MASH in an A 1 R-dependent manner. These results highlight that hepatic A 1 R is a potential target for MAFL/ MASH therapy.
WOS关键词PROTEIN-KINASE-A ; FATTY LIVER-DISEASE ; A(1) ADENOSINE RECEPTOR ; SCAP/SREBP PATHWAY ; LIPID-METABOLISM ; GENE-EXPRESSION ; MOUSE MODEL ; CYCLIC-AMP ; T-CELLS ; PHOSPHORYLATION
资助项目National Natural Science Foundation of China[81873059] ; National Natural Science Foundation of China[82374129] ; National Nat-ural Science Foundation of China[U21A20413] ; Shanghai Excellent Academic Leaders Program[21XD1403500] ; State Administration of TCM
WOS研究方向Cell Biology ; Research & Experimental Medicine
语种英语
WOS记录号WOS:001222576300001
出版者CELL PRESS
源URL[http://119.78.100.183/handle/2S10ELR8/311346]  
专题新药研究国家重点实验室
通讯作者Hong, Ying; He, Xiaofang; Li, Yan; Li, Mingxiao; Zhong, Jing; Sheng, Lili; Li, Houkai
作者单位1.Huzhou Univ, Huzhou Cent Hosp, Affiliated Cent Hosp, Dept Hepatobiliary Surg, Huzhou 313000, Peoples R China
2.Hong Kong Baptist Univ, Sch Chinese Med, Kowloon Tong, Hong Kong 999077, Peoples R China
3.Chinese Acad Agr Sci, Shanghai Vet Res Inst, Key Lab Vet Chem Drugs & Pharmaceut, Minist Agr & Rural Affairs, Shanghai 200241, Peoples R China
4.Shanghai Univ Tradit Chinese Med, Inst Interdisciplinary Integrat Med Res, Shanghai Frontiers Sci Ctr TCM Chem Biol, Shanghai 201203, Peoples R China
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
6.Huzhou Univ, Huzhou Cent Hosp, Affiliated Cent Hosp, Dept Pathol, Huzhou 313000, Peoples R China
7.Huzhou Univ, Huzhou Cent Hosp, Affiliated Cent Hosp, Huzhou Key Lab Precis Med Res & Translat Infect Di, Huzhou 313000, Peoples R China
8.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Zhu, Weize,Hong, Ying,Tong, Zhaowei,et al. Article Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation[J]. CELL REPORTS MEDICINE,2024,5(3):25.
APA Zhu, Weize.,Hong, Ying.,Tong, Zhaowei.,He, Xiaofang.,Li, Yan.,...&Li, Houkai.(2024).Article Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation.CELL REPORTS MEDICINE,5(3),25.
MLA Zhu, Weize,et al."Article Activation of hepatic adenosine A1 receptor ameliorates MASH via inhibiting SREBPs maturation".CELL REPORTS MEDICINE 5.3(2024):25.

入库方式： OAI收割

来源：上海药物研究所

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