Open AccessDeficiency in intestinal epithelial O‐GlcNAcylation predisposes to gut inflammation
Author(s) -
Zhao Ming,
Xiong Xiwen,
Ren Kaiqun,
Xu Bing,
Cheng Meng,
Sahu Chinmayi,
Wu Kaichun,
Nie Yongzhan,
Huang Zan,
Blumberg Richard S,
Han Xiaonan,
Ruan HaiBin
Publication year - 2018
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201708736
Subject(s) - dysbiosis , inflammation , homeostasis , colitis , intestinal mucosa , inflammatory bowel disease , biology , paneth cell , intracellular , microbiology and biotechnology , immunology , biochemistry , gut flora , medicine , disease , small intestine
Post‐translational modifications in intestinal epithelial cells ( IEC s) allow for precise control in intestinal homeostasis, the breakdown of which may precipitate the pathological damage and inflammation in inflammatory bowel disease. The O‐linked β‐N‐acetylglucosamine (O‐Glc NA c) modification on intracellular proteins controls diverse biological processes; however, its roles in intestinal homeostasis are still largely unexplored. Here, we found that levels of protein O‐Glc NA cylation and the expression of O‐Glc NA c transferase ( OGT ), the enzyme adding the O‐Glc NA c moiety, were reduced in IEC s in human IBD patients. Deletion of OGT specifically in IEC s resulted in disrupted epithelial barrier, microbial dysbiosis, Paneth cell dysfunction, and intestinal inflammation in mice. Using fecal microbiota transplantation in mice, we demonstrated that microbial dysbiosis although was insufficient to induce spontaneous inflammation but exacerbated chemical‐induced colitis. Paneth cell‐specific deletion of OGT led to Paneth cell dysfunction, which might predispose mice to chemical‐induced colitis. On the other hand, the augmentation of O‐Glc NA c signaling by inhibiting O‐Glc NA case, the enzyme removing O‐Glc NA cylation, alleviated chemical‐induced colitis. Our data reveal that protein O‐Glc NA cylation in IEC s controls key regulatory mechanisms to maintain mucosal homeostasis.