Possible roles of galectin-2-mucin interaction in the gastric mucosal barrier

• Project/Area Number: 18K06634
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 47030:Pharmaceutical hygiene and biochemistry-related
• Research Institution: Teikyo University
• Principal Investigator: Arata Yoichiro 帝京大学, 薬学部, 教授 (90246017)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: ガレクチン / Gal-2 / ムチン / MUC5AC / 胃 / ガレクチン-2 / 糖鎖 / 粘膜 / S-ニトロソ化

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.

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。

Research Products

• [Journal Article] Potential Interaction between Galectin-2 and MUC5AC in Mouse Gastric Mucus (2020)
  • Author(s): Tamura, M., Tanaka, T., Fujii, N., Tanikawa, T., Oka, O., Takeuchi, T., Hatanaka, T., Kishimoto, S., Arata, Y.
  • Journal Title: Biological and Pharmaceutical Bulletin Volume: 43 Issue: 2 Pages: 356-360
  • DOI: 10.1248/bpb.b19-00705
  • NAID: 130007793783
  • ISSN: 0918-6158, 1347-5215
  • Year and Date: 2020-02-01
  • Peer Reviewed / Open Access
• [Journal Article] Expression, S-nitrosylation, and measurement of S-nitrosylation ratio of recombinant galectin-2. (2020)
  • Author(s): Tamura, M. and Arata, Y.
  • Journal Title: Methods Mol Biol. Volume: 2132 Pages: 55-63
  • DOI: 10.1007/978-1-0716-0430-4_6
  • ISBN: 9781071604298, 9781071604304
  • Peer Reviewed
• [Journal Article] Galectin-2 has bactericidal effects against Helicobacter pylori in a β-galactoside-dependent manner. (2020)
  • Author(s): Sasaki, T., Saito, R., Oyama, M., Takeuchi, T., Tanaka, T., Natsume, H., Tamura, M., Arata, Y., Hatanaka, T.
  • Journal Title: Int. J. Mol. Sci. Volume: 21 Issue: 8 Pages: 2697-2697
  • DOI: 10.3390/ijms21082697
  • NAID: 120006881346
  • Peer Reviewed / Open Access
• [Journal Article] Galectin-2 suppresses nematode development by binding to the invertebrate-specific galactoseβ1-4fucose glyco-epitope. (2019)
  • Author(s): Takeuchi, T. Tamura, M., Ishiwata, K., Hamasaki, M., Hamano, S., Arata, Y., Hatanaka, T.
  • Journal Title: Glycobiology Volume: 29 Issue: 6 Pages: 504-512
  • DOI: 10.1093/glycob/cwz022
  • NAID: 120006871140
  • Peer Reviewed
• [Presentation] ガレクチン-2の酸化的失活からの保護におけるリガンドの役割 (2021)
  • Author(s): 田村真由美、谷川尚、岡沙織、武内智春、畑中朋美、荒田洋一郎
  • Organizer: 日本薬学会第141年会
• [Presentation] Helicobacter pyloriに対するガレクチン-2とガレクチン-3の影響の比較 (2021)
  • Author(s): 佐々木啓晴、大山翠、田村真由美、武内智春、田中享、一色恭徳、荒田洋一郎、畑中朋美
  • Organizer: 日本薬学会第141年会
• [Presentation] S-ニトロソ化と酸化により活性制御を受けるガレクチン-2のリガンド候補の探索 (2020)
  • Author(s): 田村真由美、田中享、藤井智彦、谷川尚、岡沙織、武内智春、畑中朋美、岸本成史、荒田洋一郎
  • Organizer: 第39回日本糖質学会年会
• [Presentation] マウスガレクチン-2の胃粘液中のリガンドの同定 (2020)
  • Author(s): 田村真由美、田中享、藤井智彦、谷川尚、岡沙織、武内智春、畑中朋美、岸本成史、荒田洋一郎
  • Organizer: 日本薬学会第140年会
• [Presentation] ガレクチン-2はマウス胃粘液由来ムチンMUC5ACと相互作用する (2019)
  • Author(s): 田村真由美、田中享、藤井智彦、谷川尚、岡沙織、武内智春、畑中朋美、岸本成史、荒田洋一郎
  • Organizer: 第38回日本糖質学会年会
• [Presentation] Possible molecular mechanisms for preventing galectin-2 inactivation under oxidative environment. (2019)
  • Author(s): Mayumi Tamura, Tomoharu Takeuchi, Tomomi Hatanaka, Yoichiro Arata
  • Organizer: 第25回国際複合糖質シンポジウム(GLYCO XXV)
  • Int'l Joint Research