TRIM34 attenuates colon inflammation and tumorigenesis by sustaining barrier integrity  

作　　者：Qiaoshi Lian Shanshan Yan Qi Yin Chenghua Yan Wanwei Zheng Wangpeng Gu Xinhao Zhao Weiguo Fan Xuezhen Li Liyan Ma Zhiyang Ling Yaguang Zhang Jie Liu Jinsong Li Bing Sun 

机构地区：[1]State Key Laboratory of Cell Biology,CAS Center for Excellence in Molecular Cell Science,Shanghai Institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,University of Chinese Academy of Sciences,320 Yueyang Road,Shanghai,200031,China [2]School of Life Sciences,University of Science and Technology of China,Hefei,230022,China [3]State Key Laboratory of Cell Biology,Shanghai Key Laboratory of Molecular Andrology,CAS Center for Excellence in Molecular Cell Science,Shanghai institute of Biochemistry and Cell Biology,Chinese Academy of Sciences,University of Chinese Academy of Sciences,320 Yueyang Road,Shanghai,200031,China [4]Department of Digestive Diseases,Huashan Hospital,Fudan University,12 Middle Wulumuqi Road,Shanghai,200040,China [5]Institutes of Biomedical Sciences and Department of Immunology,Shanghai Medical School,Fudan University,138 Yi Xue Yuan Road,Shanghai,200032,China

出　　处：《Cellular & Molecular Immunology》2021年第2期350-362,共13页中国免疫学杂志（英文版）

基　　金：We thank Dangsheng Li for critical suggestions.We are grateful to Guomei Lin for breeding the animals and Li Li for animal management.We also acknowledge the individuals involved in technical support at the Core Facility for Cell Biology and the Animal Core Facility.This work was supported by grants from the National Key Research and Development Program of China(2018YFA0507402);the National Natural Science Foundation of China(31230024);the Chinese Academy of Sciences(XDB19000000);the National Natural Science Foundation of China(81761128009 and 81630016).

摘　　要：Loss of the colonic inner mucus layer leads to spontaneously severe colitis and colorectal cancer.However,key host factors that may control the generation of the inner mucus layer are rarely reported.Here,we identify a novel function of TRIM34 in goblet cells(GCs)in controlling inner mucus layer generation.Upon DSS treatment,TRIM34 deficiency led to a reduction in Muc2 secretion by GCs and subsequent defects in the inner mucus layer.This outcome rendered TRIM34-deficient mice more susceptible to DSS-induced colitis and colitis-associated colorectal cancer.Mechanistic experiments demonstrated that TRIM34 controlled TLR signaling-induced Nox/Duox-dependent ROS synthesis,thereby promoting the compound exocytosis of Muc2 by colonic GCs that were exposed to bacterial TLR ligands.Clinical analysis revealed that TRIM34 levels in patient samples were correlated with the outcome of ulcerative colitis(UC)and the prognosis of rectal adenocarcinoma.This study indicates that TRIM34 expression in GCs plays an essential role in generating the inner mucus layer and preventing excessive colon inflammation and tumorigenesis.

关 键 词：Colon inflammation Goblet cell Toll-like receptor TRIM34 MUC2 

分 类 号：R574.62[医药卫生—消化系统]