Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation

Ming Zhao, Xiwen Xiong, Kaiqun Ren, Bing Xu, Meng Cheng, CHINMAYI S SAHU, Kaichun Wu, Yongzhan Nie, Zan Huang, Richard S. Blumberg, Xiaonan Han, Hai-Bin Ruan

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

Post-translational modifications in intestinal epithelial cells (IECs) 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-GlcNAc) 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-GlcNAcylation and the expression of O-GlcNAc transferase (OGT), the enzyme adding the O-GlcNAc moiety, were reduced in IECs in human IBD patients. Deletion of OGT specifically in IECs 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-GlcNAc signaling by inhibiting O-GlcNAcase, the enzyme removing O-GlcNAcylation, alleviated chemical-induced colitis. Our data reveal that protein O-GlcNAcylation in IECs controls key regulatory mechanisms to maintain mucosal homeostasis.

Original languageEnglish (US)
Article numbere8736
JournalEMBO Molecular Medicine
Volume10
Issue number8
DOIs
StatePublished - Aug 2018

Bibliographical note

Publisher Copyright:
© 2018 The Authors. Published under the terms of the CC BY 4.0 license

Keywords

  • Paneth cells
  • STAT signaling
  • epithelial barrier function
  • gut microbiota
  • inflammatory bowel disease

Fingerprint

Dive into the research topics of 'Deficiency in intestinal epithelial O-GlcNAcylation predisposes to gut inflammation'. Together they form a unique fingerprint.

Cite this