論文 - 詳細
| RRC ID | 5994 |
|---|---|
| 著者 | Tobisawa Y, Imai Y, Fukuda M, Kawashima H. |
| タイトル | Sulfation of colonic mucins by N-acetylglucosamine 6-O-sulfotransferase-2 and its protective function in experimental colitis in mice. |
| ジャーナル | J Biol Chem |
| Abstract |
N-Acetylglucosamine 6-O-sulfotransferase-2 (GlcNAc6ST-2) catalyzes the sulfation of mucin-like glycoproteins, which function as ligands for a lymphocyte homing receptor, L-selectin, in the lymph node high endothelial venules (HEVs). We previously showed that GlcNAc6ST-2 is expressed not only in lymph node HEVs but also in the colonic epithelial cells in mice. Here we investigated the regulatory mechanism and physiological significance of colonic expression of GlcNAc6ST-2 in mice. Treatment of a mouse colonic epithelial cell line with butyrate, a short-chain fatty acid produced by anaerobic bacteria, induced GlcNAc6ST-2 expression in the presence of epidermal growth factor. Administration of butyrate in the drinking water stimulated GlcNAc6ST-2 expression in the mouse intestine, indicating that butyrate could serve as a regulatory molecule for the GlcNAc6ST-2 expression in vivo. Immunohistochemical analysis indicated that the sulfation of colonic mucins was greatly diminished in GlcNAc6ST-2-deficient mice. Liquid chromatography coupled to electrospray ionization tandem mass spectrometry of the colonic-mucin O-glycans from wild-type and GlcNAc6ST-2-deficient mice showed that GlcNAc-6-O-sulfation was the predominant sulfate modification of these mucins, and it was exclusively mediated by GlcNAc6ST-2. After colitis induction by dextran sulfate sodium, significantly more leukocyte infiltration was observed in the colon of GlcNAc6ST-2-deficient mice than in that of wild-type mice, indicating that the sulfation of colonic mucins by GlcNAc6ST-2 has a protective function in experimental colitis. These findings indicate that GlcNAc6ST-2, whose expression is regulated by butyrate, is a major sulfotransferase in the biosynthesis of sulfomucins in the mouse colon, where they serve as a mucosal barrier against colonic inflammation. |
| 巻・号 | 285(9) |
| ページ | 6750-60 |
| 公開日 | 2010-2-26 |
| DOI | 10.1074/jbc.M109.067082 |
| PII | S0021-9258(19)37840-8 |
| PMID | 20018871 |
| PMC | PMC2825469 |
| MeSH | Animals Butyrates / pharmacology Chemotaxis, Leukocyte Colitis / enzymology Colitis / metabolism* Colon / metabolism* Colon / pathology Disease Models, Animal Leukocytes / pathology Mice Mucins / metabolism* Sulfates / metabolism* Sulfotransferases / metabolism* |
| IF | 4.238 |
| 引用数 | 52 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
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| 最多言及媒体 | Blogs |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 実験動物マウス | RBRC01361 |