Heparan sulfate and heparanase are involved in viral pathological processes
| Project/Area Number |
16K08342
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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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| Research Field |
Environmental and hygienic pharmacy
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| Research Institution | Hoshi University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
安達 勇光 公益財団法人微生物化学研究会, 微生物化学研究所 沼津支所, 主席研究員 (00250051)
山本 典生 順天堂大学, 医学部, 准教授 (40323703)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 微生物・感染症学 / 細胞外マトリックス / 炎症 / インフルエンザウイルス / ヘパラナーゼ / 上皮細胞 / 組織修復 / ヘパラン硫酸 / プロテオグリカン / マスト細胞 / ウイルス |
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| Outline of Final Research Achievements |
Heparan sulfate and a sole degrading enzyme heparanase are involved in infectious and subsequent pathological processes of influenza virus. Lack of syndecan-1 expression in lung epithelial cells increased infection efficiency of influenza virus. Heparastatin (SF4) and another novel heparanase inhibitor as an endogenous molecule (chondroitin sulfates) have been identified and examined for suppression of infection-associated inflammation. A cell surface molecule syndecan-4 is involved in the incorporation process of extracellular heparanase into mast cells. Survival of epithelial cells is enhanced via heparanase- and cleaved heparan sulfate-mediated stimuli in which an NF-kappaB-dependent intracellular signal is partly involved. The present research project demonstrates potential availability of heparanase inhibitors as a drug candidate to suppress pathological disorders induced by influenza virus infection.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究課題の実施により、インフルエンザウイルス感染時におけるヘパラナーゼとヘパラン硫酸の役割の一端を示すことができた。ウイルスの感染過程とともに、これに伴って生じる個体内の炎症や組織破壊についても、ヘパラナーゼとヘパラン硫酸は病態を調節する上で重要な因子であった。このことはヘパラナーゼによるヘパラン硫酸分解の制御方法の開発が重要であることを改めて示すものであり、阻害剤を開発する上での動機付けを高めた。新型コロナウイルス感染症でも示されたように、感染防御とともに、これに随伴して生じる局所性もしくは全身性の炎症症状に対して、その制御方法を見出すことは極めて重要な課題である。
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Report
(5 results)
Research Products
(52 results)
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[Journal Article] Chondroitin sulfate E blocks enzymatic action of heparanase and heparanase-induced cellular responses.2019
Author(s)
Higashi N, Maeda R, Sesoko N, Isono M, Ishikawa S, Tani Y, Takahashi K, Oku T, Higashi K, Onishi S, Nakajima M, Irimura T.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 520
Issue: 1
Pages: 152-158
DOI
Related Report
Peer Reviewed
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[Journal Article] Incorporation, intracellular trafficking and processing of extracellular heparanase by mast cells: involvement of syndecan 4-dependent pathway.2018
Author(s)
Higashi N, Waki M, Sudo Y, Suzuki S, Oku T, Tsuiji M, Tsuji T, Miyagishi M, Takahashi K, Nakajima M and Irimura T.
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Journal Title
Biochem. Biophys. Res. Commun.
Volume: 503
Issue: 4
Pages: 3235-3241
DOI
Related Report
Peer Reviewed
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[Journal Article] Microbial metabolites and derivatives targeted at inflammation and bone diseases therapy: chemistry, biological activity and pharmacology.2018
Author(s)
Adachi H, Nakae K, Sakamoto S, Nosaka C, Atsumi S, Shibuya M, Higashi N, Nakajima M, Irimura T, Nishimura Y.
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Journal Title
J Antibiot (Tokyo).
Volume: 71
Issue: 1
Pages: 60-71
DOI
Related Report
Peer Reviewed
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[Journal Article] A humanized mouse model identifies key amino acids for low immunogenicity of H7N9 vaccines.2017
Author(s)
Wada Y, Nithichanon A, Nobusawa E, Moise L, Martin W, Yamamoto N, Terahara K, Hagiwara H, Odagiri T, Tashiro M, Lertmemongkolchai G, Takeyama H, Groot AD, Ato M, Takahashi Y.
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Journal Title
Sci. Rep.
Volume: 7
Issue: 1
Pages: 1283-1283
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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