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Cleavage of sulfated glycan as a regulatory event for inflammatory responses to infection and chemical compounds

Research Project

Project/Area Number 25460165
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Environmental and hygienic pharmacy
Research InstitutionHoshi University (2016)
The University of Tokyo (2013-2015)

Principal Investigator

Higashi Nobuaki  星薬科大学, 薬学部, 教授 (40302616)

Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords環境系薬学 / 感染 / 炎症 / 好中球 / マスト細胞 / 細胞外マトリックス / ヘパラナーゼ / ケモカイン / 微生物・感染症学 / アレルギー / 敗血症 / 上皮細胞 / マトリックスメタロプロテアーゼ / 脱顆粒
Outline of Final Research Achievements

Acute inflammation as a cause of infection occasionally expands to whole body, which gives rise to fatal systemic infection. Apart from previous approaches focusing on identification of critical mediators, our focus is on microenvironments that help a variety of mediators’ action, also degrading process of extracellular matrices. Heparanase is an enzyme involved in basement membrane degradation as well as enhanced release of inflammatory mediators resulting from cleavage of heparan sulfate. Our goal is to elucidate how inflammatory reaction is regulated by cleavage of sulfated carbohydrates, also to suppress inflammation through inhibition of heparanase activity. We examined a novel regulatory mechanism of inflammation of via cleavage of heparin sulfate/heparin, therapeutic effect of a heparanase inhibitor on inflammatory diseases, and a novel proinflammatory cytokine-like action of heparanase.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (26 results)

All 2017 2016 2015 2014 2013 Other

All Int'l Joint Research (1 results) Journal Article (7 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 4 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (18 results) (of which Int'l Joint Research: 2 results,  Invited: 3 results)

  • [Int'l Joint Research] Institute of Zoology/Jagiellonian University(Poland)

    • Related Report
      2015 Research-status Report
  • [Journal Article] 上皮細胞の恒常性維持におけるヘパラン硫酸とヘパラナーゼの役割2017

    • Author(s)
      東 伸昭
    • Journal Title

      アレルギーの臨床

      Volume: 37 Pages: 300-302

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Heparanase augments inflammatory chemokine production from colorectal carcinoma cell lines.2016

    • Author(s)
      Tsunekawa N, Higashi N, Kogane Y, Waki M, Shida H, Nishimura Y, Adachi H, Nakajima M, Irimura T
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 469 Issue: 4 Pages: 878-883

    • DOI

      10.1016/j.bbrc.2015.12.074

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] An iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouches.2016

    • Author(s)
      Sue M, Higashi N, Shida H, Kogane Y, Nishimura Y, Adachi H, Kolaczkowska E, Kepka M, Nakajima M, Irimura T.
    • Journal Title

      Int Immunopharmacol

      Volume: 35 Pages: 15-21

    • DOI

      10.1016/j.intimp.2016.03.017

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] POMGNT1 Is Glycosylated by Mucin-Type <i>O</i>-Glycans2015

    • Author(s)
      Xin X, Akasaka-Manya K, Manya H, Furukawa J, Kuwahara N, Okada K, Tsumoto H, Higashi N, Kato R, Shinohara Y, Irimura T, Endo T.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 38 Issue: 9 Pages: 1389-1394

    • DOI

      10.1248/bpb.b15-00415

    • NAID

      130005096979

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 硫酸化糖鎖ヘパリンと糖鎖切断酵素ヘパラナーゼはマスト細胞の機能を変える2015

    • Author(s)
      東 伸昭
    • Journal Title

      アレルギーの臨床

      Volume: 35 Pages: 1169-1173

    • Related Report
      2015 Research-status Report
  • [Journal Article] 糖鎖切断酵素ヘパラナーゼは免疫細胞の移動ツールである2015

    • Author(s)
      東 伸昭
    • Journal Title

      アレルギーの臨床

      Volume: 35 Pages: 1368-1371

    • Related Report
      2015 Research-status Report
  • [Journal Article] Heparanase-mediated cleavage of macromolecular heparin accelerates release of granular components of mast cells from extracellular matrices.2014

    • Author(s)
      Higashi N, Waki M, Sue M, Kogane Y, Shida H, Tsunekawa N, Hasan A, Sato T, Kitahara A, Kasaoka T, Hayakawa Y, Nakajima M, Irimura T.
    • Journal Title

      Biochemical Jornal

      Volume: 458(2) Issue: 2 Pages: 291-9

    • DOI

      10.1042/bj20131463

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] 顆粒内糖鎖ヘパリンの切断酵素ヘパラナーゼはマスト細胞に取り込まれて機能する2017

    • Author(s)
      東 伸昭、中島元夫、入村達郎
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台国際センター(仙台)
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] マスト細胞が分泌顆粒内に保持する硫酸化糖鎖とヘパラナーゼ2017

    • Author(s)
      東 伸昭
    • Organizer
      Glycoimmunology 2017
    • Place of Presentation
      東京医科歯科大学(東京)
    • Year and Date
      2017-01-26
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ヘパラナーゼによる硫酸化糖鎖の切断と免疫細胞の機能調節2016

    • Author(s)
      東 伸昭
    • Organizer
      GlycoTokyo2016
    • Place of Presentation
      東京工業大学大岡山キャンパス(東京)
    • Year and Date
      2016-11-19
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ヘパラナーゼ阻害物質heparastatin(SF4) は炎症細胞の浸潤と基底膜ヘパラン硫酸分解を抑制する2016

    • Author(s)
      東 伸昭、須江真由美、志田拓顕、小金裕介、西村吉雄、安達勇光、Elzbieta Kolaczkowska、Magdalena Kepka、中島元夫、入村達郎
    • Organizer
      第35回日本糖質学会年会
    • Place of Presentation
      高知市文化プラザかるぽーと(高知)
    • Year and Date
      2016-09-01
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヘパラナーゼは大腸癌細胞のケモカイン産生を増強する2016

    • Author(s)
      東 伸昭、中島元夫、入村達郎
    • Organizer
      第25回日本がん転移学会学術集会
    • Place of Presentation
      米子コンベンションセンター(米子)
    • Year and Date
      2016-07-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] An Iminosugar-based heparanase inhibitor heparastatin (SF4) suppresses infiltration of neutrophils and monocytes into inflamed dorsal air pouches.2016

    • Author(s)
      Nobuaki Higashi, Mayumi Sue, Hiroaki Shida, Yusuke Kogane, Yoshio Nishimura, Hayamitsu Adachi, Elzbieta Kolaczkowska, Magdalena Kepka, Motowo Nakajima, Tatsuro Irimura
    • Organizer
      The 24th International Symposium on Molecular Cell Biology of Macrophages
    • Place of Presentation
      ソラシティ・カンファレンスセンター(東京)
    • Year and Date
      2016-06-04
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヘパラナーゼ阻害物質は好中球の浸潤と基底膜ヘパラン硫酸分解を抑制する2016

    • Author(s)
      東 伸昭、須江真由美、志田拓顕、西村吉雄、安達勇光、中島元夫、入村達郎
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-03-29
    • Related Report
      2015 Research-status Report
  • [Presentation] 細胞外マトリックスの場で免疫細胞の機能を調節するヘパラナーゼ2015

    • Author(s)
      東 伸昭
    • Organizer
      Glyco-immunology 2015
    • Place of Presentation
      東京医科歯科大学(東京都文京区)
    • Year and Date
      2015-08-20
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] ヘパラナーゼはヘパラン硫酸を介して大腸癌細胞株のケモカイン産生を亢進する2015

    • Author(s)
      東 伸昭、恒川直輝、中島元夫、入村達郎
    • Organizer
      第34回日本糖質学会年会
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2015-08-02
    • Related Report
      2015 Research-status Report
  • [Presentation] Heparanase augments inflammatory chemokine production in colorectal carcinoma cell lines.2015

    • Author(s)
      Nobuaki Higashi, Naoki Tsunekawa, Yusuke Kogane, Yoshio Nishimura, Hayamitsu Adachi, Motowo Nakajima, Tatsuro Irimura
    • Organizer
      International Conference of Cancer Immunotherapy and Macrophages 2015
    • Place of Presentation
      東京大学(東京都文京区)
    • Year and Date
      2015-07-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Heparanase-mediated cleavage of macromolecular heparin accelerates release of granular components of mouse peritoneal cell-derived mast cells.2014

    • Author(s)
      Nobuaki Higashi, Tatsuro Irimura
    • Organizer
      第43回日本免疫学会学術集会
    • Place of Presentation
      国立京都国際会館、京都
    • Year and Date
      2014-12-10 – 2014-12-12
    • Related Report
      2014 Research-status Report
  • [Presentation] マスト細胞分泌顆粒内ヘパリンの切断は細胞外マトリックスからの生理活性物質の放出を促進する2014

    • Author(s)
      東 伸昭、中島元夫、入村達郎
    • Organizer
      第33回日本糖質学会年会
    • Place of Presentation
      国立大学法人名古屋大学、名古屋
    • Year and Date
      2014-08-10 – 2014-08-12
    • Related Report
      2014 Research-status Report
  • [Presentation] 結腸がんの転移微小環境におけるヘパラナーゼ:ヘパラナーゼによる転移関連分子の発現誘導とその抑制の試み2014

    • Author(s)
      東 伸昭、恒川直輝、中島元夫、入村達郎
    • Organizer
      第23回日本がん転移学会学術集会
    • Place of Presentation
      金沢市文化ホール・金沢ニューグランドホテル、金沢
    • Year and Date
      2014-07-10 – 2014-07-11
    • Related Report
      2014 Research-status Report
  • [Presentation] 結腸がんの転移微小環境におけるヘパラナーゼ:ケモカイン産生誘導における役割2013

    • Author(s)
      恒川直輝、東伸昭、中島元夫、入村達郎
    • Organizer
      第22回日本がん転移学会学術集会
    • Place of Presentation
      ホテルブエナビスタ松本・長野
    • Related Report
      2013 Research-status Report
  • [Presentation] ヘパラナーゼは結腸がん細胞株に作用し転移関連分子の発現を誘導する2013

    • Author(s)
      恒川直輝、東伸昭、中島元夫、入村達郎
    • Organizer
      第32回日本糖質学会年会
    • Place of Presentation
      大阪国際交流センター・大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] 結腸がんの転移微小環境におけるヘパラナーゼの関与2013

    • Author(s)
      恒川直輝、東伸昭、中島元夫、入村達郎
    • Organizer
      第18回日本病態プロテアーゼ学会学術集会
    • Place of Presentation
      千里ライフサイエンスセンター・大阪
    • Related Report
      2013 Research-status Report
  • [Presentation] The role of heparanase in the change of chemokine expressions in colon cancer cells2013

    • Author(s)
      Naoki Tsunekawa, Nobuaki Higashi, Tatsuro Irimura
    • Organizer
      第42回日本免疫学会学術集会
    • Place of Presentation
      幕張メッセ、千葉
    • Related Report
      2013 Research-status Report
  • [Presentation] 結腸がんの転移微小環境におけるヘパラナーゼ:ケモカインの発現誘導における役割

    • Author(s)
      恒川直輝、東 伸昭、中島元夫、入村達郎
    • Organizer
      第14回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      日本薬学会長井記念ホール・東京
    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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