Augmented O-GlcNAcylation alleviates inflammation-mediated colon carcinogenesis via suppression of acute inflammation

作者：Hirata Yoshimasa; Nakagawa Takatoshi^*; Moriwaki Kazumasa; Koubayashi Eiko; Kakimoto Kazuki; Takeuchi Toshihisa; Inoue Takuya; Higuchi Kazuhide; Asahi Michio^*

来源：Journal of Clinical Biochemistry and Nutrition, 2018, 62(3): 221-229.

DOI：10.3164/jcbn.17-106

• O-GlcNAcylation
• Ogt-Tg
• colon carcinogenesis
• inflammation
• NF-kappa B

Colon cancer prevalence is high worldwide. O-GlcNAcylation has been associated with tumor growth in various tissues, including the colon; however, its link to carcinogenesis is not fully understood. We investigated the association of O-GlcNAcylation with colon carcinogenesis using a 1,2-dimethylhydrazine/dextran sodium sulfate-induced colon carcinogenesis model in wild type and O-GlcNAc transferase-transgenic (Ogt-Tg) mice. The incidence of colon cancer was significantly lower in Ogt-Tg than in wild type mice. The colonic length was not shortened in Ogt-Tg mice, and NF-kappa B p65 phosphorylation was strongly suppressed, indicating that reduction of inflammation might be related to the alleviation of colon carcinogenesis. Dextran sodium sulfate-induced acute colitis mice were used to evaluate the effect of O-GlcNAcylation on inflammation at the maximal inflammation period. In Ogt-Tg mice, NF-kappa B p65 phosphorylation and interleukin-1 beta mRNA expression were suppressed. Histochemical staining demonstrated shedding of colon epithelial cells in wild type mice a few days after dextran sodium sulfate treatment, whereas they remained essentially intact in Ogt-Tg mice. There were no significant differences on histochemical staining in the remaining epithelia between groups. These data suggest that O-GlcNAcylation could prevent colon carcinogenesis through reducing acute maximum inflammation, suggesting modulation of O-GlcNAcylation as a novel therapeutic optio.

• 出版日期2018-5-1