Role of glycine N-methyltransferase in experimental ulcerative colitis.
OBJECTIVE
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.
Department of Physiology, School of Medicine, National Yang-Ming University, Taipei, Taiwan.
Wen-Yueh
WY
Chou
Jin-Feng
JF
Zhao
Yi-Ming Arthur
YM
Chen
Kuan-I
KI
Lee
Kuo-Hui
KH
Su
Song-Kun
SK
Shyue
Tzong-Shyuan
TS
Lee
D000818:Animals; D003093:Colitis, Ulcerative / Q000139:chemically induced / Q000235:genetics* / Q000473:pathology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D050938:Glycine N-Methyltransferase / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D058990:Molecular Targeted Therapy
D018836:Inflammation Mediators; D016264:Dextran Sulfate; D050938:Glycine N-Methyltransferase
GNMT; colitis; dextran sulfate sodium; inflammation