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The host-parasite relationship mediated by Strongyloides venestatin/RAGE axis

Research Project

Project/Area Number 18K15140
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 49040:Parasitology-related
Research InstitutionKitasato University

Principal Investigator

Tsubokawa Daigo  北里大学, 医学部, 助教 (30714901)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords蠕虫 / 宿主応答 / 幼虫体内移行 / カルシウム結合タンパク質 / RAGE / 糞線虫 / ベネスタチン / RNA干渉 / 体内移行 / カルシウム結合蛋白 / ES物質
Outline of Final Research Achievements

In this study, we evaluated the effects of venestatin, an EF-hand Ca2+-binding protein secreted by the parasitic helminth Strongyloides venezuelensis, on RAGE activity and immune responses. Our results demonstrated that venestatin bound to RAGE and downregulated the host immune response. Venestatin suppressed RAGE-mediated immune responses in host skin induced by helminthic infection, thereby promoting larval migration. The anti-inflammatory mechanism of venestatin may be targeted for the development of anthelminthics and immunosuppressive agents for the treatment of RAGE-mediated inflammatory diseases.

Academic Significance and Societal Importance of the Research Achievements

近年,消化管寄生蠕虫の分泌物がマクロファージを誘導し,大腸炎モデルマウスの病態を緩和することが報告されており,寄生蠕虫が有する抗炎症物質が炎症性疾患に対する治療薬候補として注目されている。ベネスタチンのようなカルシウム結合タンパク質は多くの寄生蠕虫種に存在しているが,遺伝子単離や機能解析が成されたのはベネスタチンが世界初である。ベネスタチン/RAGEを介する抗炎症機構を解明した本研究成果は,癌,糖尿病,喘息,潰瘍性大腸炎,アルツハイマー病などのRAGE介在性炎症性疾患の新規治療法としての応用が期待できる。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (15 results)

All 2021 2019 2018 Other

All Journal Article (5 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (8 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Journal Article] Venestatin from parasitic helminths interferes with receptor for advanced glycation end products (RAGE)-mediated immune responses to promote larval migration2021

    • Author(s)
      Tsubokawa Daigo、Kikuchi Taisei、Lee Jae Man、Kusakabe Takahiro、Yamamoto Yasuhiko、Maruyama Haruhiko
    • Journal Title

      PLOS Pathogens

      Volume: 17 Issue: 6 Pages: e1009649-e1009649

    • DOI

      10.1371/journal.ppat.1009649

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of the RAGE-binding protein, Strongyloides venestatin, produced by the silkworm-baculovirus expression system.2019

    • Author(s)
      Tsubokawa D, Lee JM, Hatta T, Mikami F, Maruyama H, Arakawa T, Kusakabe T, Tsuji N
    • Journal Title

      Infect Genet Evol

      Volume: 75 Pages: 103964-103964

    • DOI

      10.1016/j.meegid.2019.103964

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 経皮侵入性線虫Strongyloides venezuelensisの宿主体内移行における終末糖化産物受容体の働き2019

    • Author(s)
      坪田理央, 坪川大悟, 八田岳士, 辻尚利
    • Journal Title

      北里医学

      Volume: 49 Pages: 111-113

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Positive phototropism is accelerated in Biomphalaria glabrata snails by infection with Schistosoma mansoni.2018

    • Author(s)
      H Maeda, T Hatta, D Tsubokawa, F Mikami, T Nishimaki, T Nakamura, Anisuzzaman, M Matsubayashi, M Ogawa, CP da Costa, N Tsuji
    • Journal Title

      Parasitology International

      Volume: 67 Issue: 5 Pages: 609-611

    • DOI

      10.1016/j.parint.2018.06.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tapeworm-related cutaneous larva migrans is caused by a cysteine protease from the larvae themselves.2018

    • Author(s)
      D Tsubokawa, T Hatta, N Tsuji
    • Journal Title

      Atlas of Science

      Volume: 15

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] ベネズエラ糞線虫の成虫寄生における終末糖化産物受容体(RAGE)の役割2019

    • Author(s)
      坪川大悟、八田岳士、小泉頌歌、関口智也、三上房子、山本靖彦、辻 尚利
    • Organizer
      第13回蠕虫研究会(宮崎)
    • Related Report
      2019 Research-status Report
  • [Presentation] マンソン住血吸虫による肉芽腫形成への終末糖化産物受容体(RAGE)の関与2019

    • Author(s)
      小泉頌歌、坪川大悟、八田岳士、三上房子、中村健、山本靖彦、辻尚利
    • Organizer
      第79回日本寄生虫学会東日本支部大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 住血吸虫症における肉芽腫性炎症と終末糖化産物受容体(RAGE)との関連2019

    • Author(s)
      小泉頌歌,坪川大悟,八田岳士,三上房子,中村健,山本靖彦,辻尚利
    • Organizer
      第60回日本熱帯医学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 糞線虫の宿主体内移行における終末糖化産物受容体(RAGE)の役割.2019

    • Author(s)
      坪川大悟、八田岳士、小泉頌歌、三上房子、山本靖彦、丸山治彦、辻尚利
    • Organizer
      第88回日本寄生虫学会(長崎)
    • Related Report
      2018 Research-status Report
  • [Presentation] 終末糖化産物受容体(RAGE)欠損マウスをもちいた蠕虫感染実験2018

    • Author(s)
      坪川大悟、小泉頌歌、八田岳士、三上房子、丸山治彦、辻尚利
    • Organizer
      第12回蠕虫研究会(湯河原)
    • Related Report
      2018 Research-status Report
  • [Presentation] ベネスタチン遺伝子ノックダウン糞線虫を用いた感染実験の展開2018

    • Author(s)
      坪川大悟、八田岳士、小泉頌歌、三上房子、辻尚利.
    • Organizer
      第26回分子寄生虫ワークショップ/第16回分子寄生虫・マラリア研究フォーラム(松山)
    • Related Report
      2018 Research-status Report
  • [Presentation] RNAi mediated suppression of venestatin in the subcutaneous migration of Strongyloides venezuelensis2018

    • Author(s)
      Daigo Tsubokawa, Takeshi Hatta, Taisei Kikuchi, Fusako Mikami, Haruhiko Maruyama and Naotoshi Tsuji
    • Organizer
      ICOPA 2018 (DAEGU, KOREA)
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ベネスタチン遺伝子ノックダウンによる糞線虫の宿主体内移行への影響2018

    • Author(s)
      坪川大悟、八田岳士、小泉頌歌、三上房子、辻尚利
    • Organizer
      第31回北里大学バイオサイエンスフォーラム(相模原)
    • Related Report
      2018 Research-status Report
  • [Remarks] リサーチマップ(坪川大悟)

    • URL

      https://researchmap.jp/daigo0525

    • Related Report
      2021 Annual Research Report
  • [Remarks] 北里大学医学部・北里大学大学院医療系研究科

    • URL

      http://web.med.kitasato-u.ac.jp/lab/parasite/research.html

    • Related Report
      2020 Research-status Report 2019 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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