TRIM27 maintains gut homeostasis by promoting intestinal stem cell self-renewal

扫码查看

原文链接

万方数据

外文摘要：Dysregulation of gut homeostasis is associated with irritable bowel syndrome(IBS),a chronic functional gastrointestinal disorder affecting approximately 11.2%of the global population.The poorly understood pathogenesis of IBS has impeded its treatment.Here,we report that the E3 ubiquitin ligase tripartite motif-containing 27(TRIM27)is weakly expressed in IBS but highly expressed in inflammatory bowel disease(IBD),a frequent chronic organic gastrointestinal disorder.Accordingly,knockout of Trim27 in mice causes spontaneously occurring IBS-like symptoms,including increased visceral hyperalgesia and abnormal stool features,as observed in IBS patients.Mechanistically,TRIM27 stabilizes β-catenin and thus activates Wnt/β-catenin signaling to promote intestinal stem cell(ISC)self-renewal.Consistent with these findings,Trim27 deficiency disrupts organoid formation,which is rescued by reintroducing TRIM27 or β-catenin.Furthermore,Wnt/β-catenin signaling activator treatment ameliorates IBS symptoms by promoting ISC self-renewal.Taken together,these data indicate that TRIM27 is critical for maintaining gut homeostasis,suggesting that targeting the TRIM27/Wnt/β-catenin axis could be a potential treatment strategy for IBS.Our study also indicates that TRIM27 might serve as a potential biomarker for differentiating IBS from IBD.

外文关键词：

TRIM27Wnt/β-catenin signalingISC self-renewalIBS

作者：

Jing Wang、Dongdong Zhao、Zehui Lei、Pupu Ge、Zhe Lu、Qiyao Chai、Yong Zhang、Lihua Qiang、Yang Yu、Xinwen Zhang、Bingxi Li、Shu Zhu、Lingqiang Zhang、Cui Hua Liu

展开 >

作者单位：

CAS Key Laboratory of Pathogenic Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China

Savaid Medical School,University of Chinese Academy of Sciences,Beijing 101408,China

State Key Laboratory of Proteomics,National Center for Protein Sciences,Beijing Institute of Lifeomics,Beijing 100850,China

Institute of Immunology,Chinese Academy of Sciences Key Laboratory of Innate Immunity and Chronic Disease,Division of Life Sciences and Medicine,University of Science and Technology of China,Hefei 230027,China

展开 >

基金：

National Key Research and Development Project of ChinaNational Key Research and Development Project of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaNational Natural Science Foundation of ChinaStrategic Priority Research Program of the Chinese Academy of SciencesYouth Innovation Promotion Association CASState Key Laboratory of ProteomicsState Key Laboratory of Proteomics

项目编号：

2021YFA13002002022YFC230290081825014318300038202204181871616XDB290200002018118SKLP-K202001SKLPO202003

出版年：

2023

DOI：

10.1038/s41423-022-00963-1

中国免疫学杂志(英文版)

中国免疫学会

中国免疫学杂志(英文版)

CSTPCDCSCDSCI

影响因子：0.731

ISSN：1672-7681

年,卷(期)：2023.20(2)

参考文献量68