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Inhibiting sorting nexin 10 promotes mucosal healing through SREBP2-mediated stemness restoration of intestinal stem cells

文献类型：期刊论文

作者Bao, Weilian7,8,9; You, Yan8,9; Ni, Jiahui8,9; Hou, Hui6; Lyu, Jiaren8,9; Feng, Guize8,9; Wang, Yirui8,9; You, Keyuan8,9; Zhang, Sulin6; Zhang, Lijie5
刊名SCIENCE ADVANCES
出版日期2023-08-01
卷号9期号:35页码:17
ISSN号2375-2548
DOI10.1126/sciadv.adh5016
通讯作者Du, Peng(dupeng@xinhuamed.com.cn) ; Chen, Daofeng(dfchen@shmu.edu.cn) ; Shen, Xiaoyan(shxiaoy@fudan.edu.cn)
英文摘要Intestinal stem cell (ISC) is a promising therapeutic target for inflammatory bowel disease. Cholesterol availability is critical for ISC stemness. Low plasma cholesterol is a typical feature of Crohn's disease (CD); however, its impact on mucosal healing remains unclear. Here, we identified an essential role of sorting nexin 10 (SNX10) in maintaining the stemness of ISCs. SNX10 expression in intestinal tissues positively correlates with the severity of human CD and mouse colitis. Conditional SNX10 knockout in intestinal epithelial cells or ISCs promotes intestinal mucosal repair by maintaining the ISC population associated with increased intracellular cholesterol synthesis. Disassociation of ERLIN2 with SCAP by SNX10 deletion enhances the activation of SREBP2, resulting in increased cholesterol biosynthesis. DC-SX029, a small-molecule inhibitor of SNX10, was used to verify the druggable potential of SNX10 for the treatment of patients with CD. Our study provides a strategy for mucosal healing through SREBP2-mediated stemness restoration of ISCs.
WOS关键词INFLAMMATORY BOWEL DISEASES ; INDUCED COLITIS ; HUMAN COLON ; IN-VITRO ; CHOLESTEROL ; ACTIVATION ; EXPRESSION ; LINKS ; HOMEOSTASIS ; INFLIXIMAB
资助项目National Natural Science Foundation of China[82130108] ; National Natural Science Foundation of China[82174044] ; National Natural Science Foundation of China[81773744] ; Shanghai Science and Technology Innovation Action Plan experimental animal research project[19140901800] ; National Health and Medical Research Council (NHMRC) of Australia[APP1163933] ; China Postdoctoral Science Foundation[BX20220069] ; China Postdoctoral Science Foundation[2021M700864]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:001059133700015
出版者AMER ASSOC ADVANCEMENT SCIENCE
源URL[http://119.78.100.183/handle/2S10ELR8/307179]  
专题新药研究国家重点实验室
通讯作者Du, Peng; Chen, Daofeng; Shen, Xiaoyan
作者单位1.Shanghai Colorectal Canc Res Ctr, Shanghai, Peoples R China
2.Shanghai Jiao Tong Univ, Sch Med, Xinhua Hosp, Dept Colorectal & Anal Surg, Shanghai, Peoples R China
3.Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen, Peoples R China
4.Univ Western Australia, Sch Biomed Sci, Perth, WA, Australia
5.Fudan Univ, Shanghai Canc Ctr, Dept Radiat Oncol, Shanghai, Peoples R China
6.Chinese Acad Sci, Shanghai Inst Mat Med, Drug Discovery & Design Ctr, State Key Lab Drug Res, Shanghai, Peoples R China
7.Fudan Univ, Sch Pharm, Dept Nat Med, Shanghai, Peoples R China
8.Fudan Univ, Sch Pharm, Key Lab Smart Drug Delivery, Minist Educ, Shanghai, Peoples R China
9.Fudan Univ, Sch Pharm, Dept Pharmacol, Minist Educ, Shanghai, Peoples R China
推荐引用方式
GB/T 7714		 Bao, Weilian,You, Yan,Ni, Jiahui,et al. Inhibiting sorting nexin 10 promotes mucosal healing through SREBP2-mediated stemness restoration of intestinal stem cells[J]. SCIENCE ADVANCES,2023,9(35):17.
APA Bao, Weilian.,You, Yan.,Ni, Jiahui.,Hou, Hui.,Lyu, Jiaren.,...&Shen, Xiaoyan.(2023).Inhibiting sorting nexin 10 promotes mucosal healing through SREBP2-mediated stemness restoration of intestinal stem cells.SCIENCE ADVANCES,9(35),17.
MLA Bao, Weilian,et al."Inhibiting sorting nexin 10 promotes mucosal healing through SREBP2-mediated stemness restoration of intestinal stem cells".SCIENCE ADVANCES 9.35(2023):17.

入库方式： OAI收割

来源：上海药物研究所

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