Role of glycine N-methyltransferase in experimental ulcerative colitis

Wen Yueh Chou, Jin Feng Zhao, Yi Ming Arthur Chen, Kuan I. Lee, Kuo Hui Su, Song Kun Shyue, Tzong Shyuan Lee

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Background and Aim: Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders with unclear etiology and mechanism(s). Glycine N-methyltransferase (GNMT) plays a central role in inflammatory diseases such as hepatitis and atherosclerosis. However, little is known about the impact of GNMT and the involved mechanism in the pathogenesis of IBD. In the current study, we investigated the role of GNMT in the mouse model of dextran sulfate sodium (DSS)-induced colitis. Methods: Protein expression was determined by Western blotting or immunohistochemistry. Histopathology was examined by hematoxylin and eosin staining. Levels of pro-inflammatory cytokines were evaluated by ELISA kits. Results: GNMT was expressed in the epithelium of the colon under normal conditions, and with DSS treatment, its expression was predominant in infiltrated leukocytes of lesions. Mice with genetic deletion of GNMT (GNMT-/-) showed increased susceptibility to DSS induction of colitis, as revealed by the progression of colitis. Additionally, severe colonic inflammation, including increased crypt loss, leukocyte infiltration, and hemorrhage, was greater with DSS treatment in GNMT-/- than wild-type mice. Furthermore, the expression of adhesion molecule and inflammatory mediators in the colon was significantly higher with DSS treatment in GNMT-/- than wild-type mice. Moreover, loss of GNMT decreased cell apoptosis in colitis lesions with DSS treatment. Conclusions: Collectively, our findings suggest that GNMT may be a crucial molecule in the pathogenesis of DSS-induced colitis. This finding may provide new information for a potential therapeutic target in treating IBD.

Original languageEnglish
Pages (from-to)494-501
Number of pages8
JournalJournal of Gastroenterology and Hepatology (Australia)
Volume29
Issue number3
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Keywords

  • Colitis
  • Dextran sulfate sodium
  • GNMT
  • Inflammation

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology

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