title: Roles of the gel-forming MUC2 mucin and its O-glycosylation in the protection against colitis and colorectal cancer.
abstract: MUC2 is the major gel-forming colonic mucin that forms the two mucus layers. Recent studies using gene-targeted mice have revealed the physiological functions of Muc2, the mouse counterpart of human MUC2, and its O-glycosylation in the colon. Muc2-deficient mice spontaneously developed colitis and colorectal cancer. As for the O-glycosylation of Muc2, conditional core 1-derived O-glycan-deficient mice in the intestines exhibited a breached inner mucus layer and spontaneously developed colitis. Similarly, core 3-derived O-glycan-deficient mice exhibited an increased susceptibility to colitis and colorectal cancer, suggesting that both core 1- and core 3-derived O-glycans on Muc2 are required for colonic protection. Mice deficient in core 2-branched O-glycans synthesized after the formation of core 1 O-glycans also exhibited increased experimental colitis. Furthermore, our recent studies using gene-targeted mice deficient in N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST)-2 revealed that sulfation of the core 2-branched O-glycans of the colonic mucins by GlcNAc6ST-2 is required for the protection against experimental colitis. Taken together, these findings demonstrate the critical roles of the MUC2 mucin and its various O-glycans in the protection against colitis and colorectal cancer. Consistently, various alterations in the expression of mucins and their O-glycosylation have been noted in clinical samples of colorectal cancer. This review focuses on the roles of the MUC2 core protein and its O-glycosylation in health and disease.
authors.affiliation: Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka 422–8526, Japan. kawashih@u-shizuoka-ken.ac.jp
authors.forename: Hiroto
authors.initials: H
authors.lastname: Kawashima
mesh_terms: D000818:Animals; D003092:Colitis / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D055262:Mucin-2 / Q000378:metabolism*; D011134:Polysaccharides / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism; D000097811:Carbohydrate Sulfotransferases
chemical_list: D055262:Mucin-2; D011134:Polysaccharides; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases