2020 Fiscal Year Final Research Report
Possible roles of galectin-2-mucin interaction in the gastric mucosal barrier
| Project/Area Number |
18K06634
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
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| Research Institution | Teikyo University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | ガレクチン / Gal-2 / ムチン / MUC5AC / 胃 |
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| Outline of Final Research Achievements |
Mucin MUC5AC was identified as a possible Gal-2 ligand in mouse gastric mucus fraction by affinity chromatography and LC/MS/MS and it was revealed that Gal-2 could interact with MUC5AC in a β-galactoside-dependent manner. In the presence of lactose, Gal-2 retained its activity under oxidative environment. The results indicated that the presence of a carbohydrate ligand as well as prevention of oxidation by S-nitrosylation could contribute towards maintaining Gal-2 activity under oxidative environment in the gastric mucosa. By immunohistochemical study, galectin-2 immunoreaction was mainly found in cytosol of gastric surface mucous cells while MUC5AC immunoreaction was found in mucosal barrier as well as in mucous granules of mucous cells. Lectin histochemical analysis using Gal-2-GFP showed glycans recognized by Gal-2 were expressed in mucous granules of mucous cells. The results suggested that Gal-2 might play a role in the secretion of MUC5AC from surface mucous cells.
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| Free Research Field |
糖鎖生物学
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| Academic Significance and Societal Importance of the Research Achievements |
胃粘膜上皮細胞によって産生される粘液中のムチンは、胃粘膜保護に重要な役割をもつ糖タンパク質である。また、ガレクチンは、β-ガラクトシドをもつ糖鎖構造を特異的に認識する動物レクチンである。胃で高発現し胃粘膜保護に関与するとされるガレクチン-2（Gal-2）は、ムチンMUC5ACと糖鎖依存的に相互作用し、胃内の酸化的環境下では、S-ニトロソ化修飾やMUC5ACなどの糖鎖との複合体形成により活性を維持すると考えられた。本研究結果により、酸化ストレス下における胃粘膜保護の新たな分子メカニズムの一端が明らかとなり、胃関連疾患防止や治療、新薬開発に向けてさらなる解析を進めることが可能になったと考えている。
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