Roles of the Gel-Forming MUC2 Mucin and Its <i>O</i>-Glycosylation in the Protection against Colitis and Colorectal Cancer
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- Kawashima Hiroto
- Laboratory of Microbiology and Immunology, School of Pharmaceutical Sciences, University of Shizuoka
Bibliographic Information
- Other Title
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- Roles of the Gel-Forming MUC2 Mucin and Its O-Glycosylation in the Protection against Colitis and Colorectal Cancer
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Description
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.
Journal
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- Biological and Pharmaceutical Bulletin
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Biological and Pharmaceutical Bulletin 35 (10), 1637-1641, 2012
The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001204633507712
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- NII Article ID
- 130001872374
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- NII Book ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC3s%2FisF2gsw%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL BIB ID
- 023972234
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- PubMed
- 23037153
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- Text Lang
- en
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- Abstract License Flag
- Disallowed