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

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 

机构地区：[1]CAS Key Laboratory of Pathogenic Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,100101,China [2]Savaid Medical School,University of Chinese Academy of Sciences,Beijing,101408,China [3]State Key Laboratory of Proteomics,National Center for Protein Sciences,Beijing Institute of Lifeomics,Beijing,100850,China [4]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

出　　处：《Cellular & Molecular Immunology》2023年第2期158-174,共17页中国免疫学杂志（英文版）

基　　金：supported by the National Key Research and Development Project of China(2021YFA1300200 to CHL and LZ,2022YFC2302900 to CHL and JW);the National Natural Science Foundation of China(81825014 to CHL,31830003 to CHL,82022041 to JW and 81871616 to JW);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB29020000 to CHL);Youth Innovation Promotion Association CAS(2018118 to JW);the State Key Laboratory of Proteomics(SKLP-K202001 to LZ and SKLPO202003 to JW).

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 stabilizesβ-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 orβ-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.

关 键 词：TRIM27 Wnt/β-catenin signaling ISC self-renewal IBS 

分 类 号：R574[医药卫生—消化系统]