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Hepatic cytochrome P450 8B1 and cholic acid potentiate intestinal epithelial injury in colitis by suppressing intestinal stem cell renewal

文献类型：期刊论文

作者Chen, Li1,10; Jiao, Tingying10; Liu, Weiwei2,3; Luo, Yuhong4; Wang, Jue5; Guo, Xiaozhen10; Tong, Xiao1,10; Lin, Zemin10; Sun, Chuying6; Wang, Kanglong10
刊名CELL STEM CELL
出版日期2022-09-01
卷号29期号:9页码:1366-+
ISSN号1934-5909
DOI10.1016/j.stem.2022.08.008
通讯作者He, Shijun(heshijun@simm.ac.cn) ; Gonzalez, Frank J.(gonzalef@mail.nih.gov) ; Xie, Cen(xiecen@simm.ac.cn)
英文摘要Although disrupted bile acid (BA) homeostasis is implicated in inflammatory bowel disease (IBD), the role of hepatic BA metabolism in the pathogenesis of colitis is poorly understood. Here, we found that cholic acid (CA) levels were increased in patients and mice. Cytochrome P450 8B1 (CYP8B1), which synthesizes CA, was induced in livers of colitic mice. CA-treated or liver Cyp8b1-overexpressing mice developed more severe colitis with compromised repair of the mucosal barrier, whereas Cyp8b1-knockout mice were resistant to colitis. Mechanistically, CA inhibited peroxisome proliferator-activated receptor alpha (PPAR alpha), resulting in impeded fatty acid oxidation (FAO) and impaired Lgr5(+) intestinal stem cell (ISC) renewal. A PPAR alpha agonist restored FAO and improved Lgr5(+) ISC function. Activation of the farnesoid X receptor (FXR) suppressed liver CYP8B1 expression and ameliorated colitis in mice. This study reveals a connection between the hepatic CYP8B1-CA axis and colitis via regulating intestinal epithelial regeneration, suggesting that BA-based strategies might be beneficial in IBD treatment.
WOS关键词FARNESOID-X-RECEPTOR ; BILE-ACIDS ; BARRIER FUNCTION ; HOMEOSTASIS ; DISEASE ; MECHANISMS ; CONTRIBUTE ; MONOLAYERS ; REPAIR ; GALL
资助项目National Key Research and Development Program of China[2021YFA1301200] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB39020600] ; Shanghai Municipal Science and Technology Major Project ; National Natural Science Foundation of China[91957116] ; National Natural Science Foundation of China[82173873] ; Shanghai Committee of Science and Technology[21S11907700] ; National Cancer Institute Intramural Research Program
WOS研究方向Cell Biology
语种英语
出版者CELL PRESS
WOS记录号WOS:000907777700001
源URL[http://119.78.100.183/handle/2S10ELR8/303881]  
专题新药研究国家重点实验室
通讯作者He, Shijun; Gonzalez, Frank J.; Xie, Cen
作者单位1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
2.Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Lab Med, Shanghai 201203, Peoples R China
3.Tongji Univ, Shanghai Tenth Peoples Hosp, Dept Lab Med & Cent Lab, Shanghai 200070, Peoples R China
4.NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA
5.Shanghai Univ Tradit Chinese Med, Longhua Hosp, Dept Nephrol, Shanghai 201203, Peoples R China
6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210029, Peoples R China
7.East China Normal Univ, Inst Biomed Sci, Shanghai Key Lab Regulatory Biol, Shanghai 200241, Peoples R China
8.Chinese Acad Sci, Univ Chinese Acad Sci, Shanghai Inst Nutr & Hlth, Shanghai Inst Biol Sci,CAS Key Lab Nutr Metab & F, Shanghai 200031, Peoples R China
9.East China Normal Univ, Sch Life Sci, Shanghai 200241, Peoples R China
10.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
推荐引用方式
GB/T 7714		 Chen, Li,Jiao, Tingying,Liu, Weiwei,et al. Hepatic cytochrome P450 8B1 and cholic acid potentiate intestinal epithelial injury in colitis by suppressing intestinal stem cell renewal[J]. CELL STEM CELL,2022,29(9):1366-+.
APA Chen, Li.,Jiao, Tingying.,Liu, Weiwei.,Luo, Yuhong.,Wang, Jue.,...&Xie, Cen.(2022).Hepatic cytochrome P450 8B1 and cholic acid potentiate intestinal epithelial injury in colitis by suppressing intestinal stem cell renewal.CELL STEM CELL,29(9),1366-+.
MLA Chen, Li,et al."Hepatic cytochrome P450 8B1 and cholic acid potentiate intestinal epithelial injury in colitis by suppressing intestinal stem cell renewal".CELL STEM CELL 29.9(2022):1366-+.

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来源：上海药物研究所

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