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Development of early diagnosis of thrombosis induced by neutrophil extracellular traps

Research Project

Project/Area Number 18K07432
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52010:General internal medicine-related
Research InstitutionHimeji Dokkyo University

Principal Investigator

Tohyama Yumi  姫路獨協大学, 薬学部, 教授 (70362770)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥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好中球 / NETs
Outline of Final Research Achievements

Neutrophil extracellular traps (NETs) formation is a biological defense mechanism in which neutrophil chromatin changes into a meshwork to capture pathogenic microorganisms. In this study, we focused on the fact that NETs stimulate platelets to induce thrombosis, and aimed to elucidate the mechanism of NETs formation and to identify the NETs components that activate platelets.
Using a knockout neutrophil model, we analyzed the intracellular chemical reactions that occur during NETs formation and found that regulation of the neutrophil cytoskeleton is essential for NETs formation. Furthermore, we are investigating two proteins that are abundant in neutrophils as candidate molecules for NETs-derived platelet activation.

Academic Significance and Societal Importance of the Research Achievements

Neutrophil extracellular traps(NETs)は、好中球のクロマチンが網状構造に変化して病原微生物を捉える生体防御機構であるが、近年、NETs成分が血小板を刺激して血栓症を誘発することが新たな病態として注目されている。
そこで本研究では、NETs形成の分子メカニズムと、NETsが血小板の活性化を介して血栓症に至るプロセスの解明に取り組んだ。研究成果の学術的意義として、好中球の細胞骨格の制御が、NETs形成に必須であることを見いだした。さらに社会的意義として、NETs由来の2種類のタンパク質を血小板活性化候補として提案した。血栓症の早期診断法の開発に寄与する。

Report

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

    (13 results)

All 2020 2019 2018

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (10 results) (of which Int'l Joint Research: 2 results)

  • [Journal Article] Syk facilitates phagosome-lysosome fusion by regulating actin-remodeling in complement-mediated phagocytosis.2020

    • Author(s)
      Tabata H, Morita H, Kaji H, Tohyama K, Tohyama Y.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 22086-22086

    • DOI

      10.1038/s41598-020-79156-7

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] KIF20A, highly expressed in immature hematopoietic cells, supports the growth of HL60 cell line2018

    • Author(s)
      Morita Hiroyuki、Matsuoka Akihito、Kida Jun-ichiro、Tabata Hiroyuki、Tohyama Kaoru、Tohyama Yumi
    • Journal Title

      International Journal of Hematology

      Volume: 108 Issue: 6 Pages: 607-614

    • DOI

      10.1007/s12185-018-2527-y

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] An MDS-derived cell line and a series of its sublines serve as an in vitro model for the leukemic evolution of MDS2018

    • Author(s)
      Kida Jun-ichiro、Tsujioka Takayuki、Suemori Shin-ichiro、Okamoto Shuichiro、Sakakibara Kanae、Takahata Takayuki、Yamauchi Takahiro、Kitanaka Akira、Tohyama Yumi、Tohyama Kaoru
    • Journal Title

      Leukemia

      Volume: 32 Issue: 8 Pages: 1846-1850

    • DOI

      10.1038/s41375-018-0189-7

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Presentation] Protein‐Tyrosine Kinase, Syk accelerates phagosome maturation by depolymerizing F‐Actin in complement‐mediated phagocytosis2020

    • Author(s)
      Hiroyuki Tabata, Yumi Tohyama
    • Organizer
      ASBMB (American Society for Biochemistry and Molecular Biology) Annual Meeting
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] チロシンキナーゼSykによるファゴソーム成熟機構の調節2019

    • Author(s)
      田畑裕幸,森田寛之,通山由美
    • Organizer
      第66回日本生化学会 近畿支部例会
    • Related Report
      2019 Research-status Report
  • [Presentation] チロシンキナーゼSykはファゴソーム膜におけるF-アクチン形成を調節する2019

    • Author(s)
      田畑裕幸, 森田寛之, 通山由美
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] CRISPR-Cas9を利用したシグナル分子ノックアウト細胞の構築とTNF-α産生への影響-ヒト白血病細胞株HL60を用いた検討2019

    • Author(s)
      柴田知明, 田畑裕幸, 通山由美
    • Organizer
      第69回日本薬学会関西支部大会
    • Related Report
      2019 Research-status Report
  • [Presentation] Syk plays an essential role in phagosome-lysosome fusion by facilitating actin-remodeling in complement mediated phagocytosis.2019

    • Author(s)
      Yumi Tohyama, Hiroyuki Tabata, Kaoru Tohyama
    • Organizer
      61st ASH(American Society of Hematology) Annual Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 好中球のNeutrophil Extracellular Traps (NETs)形成機構におけるProtein S100-A8の機能の解析2018

    • Author(s)
      森田寛之, 田畑裕幸, 通山由美
    • Organizer
      第65回日本生化学会 近畿支部例会
    • Related Report
      2018 Research-status Report
  • [Presentation] 高温処理によるStaphylococcus aureusの生存能力への影響2018

    • Author(s)
      川井眞好,通山由美
    • Organizer
      第65回日本生化学会 近畿支部例会
    • Related Report
      2018 Research-status Report
  • [Presentation] チロシンキナーゼSykによるファゴソームの酸性化の調節2018

    • Author(s)
      田畑裕幸, 森田寛之, 通山由美
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 食細胞(好中球様・マクロファージ様細胞)におけるProtein S100-A8, Protein S100-A9の機能解析: 好中球様・マクロファージ様に分化したヒト白血病細胞株HL60による検討2018

    • Author(s)
      森田寛之, 田畑裕幸, 通山由美
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 食作用依存性のMPO活性化におけるチロシンキナーゼSykの機能解析:好中球様に分化したヒト白血病細胞株HL60による検討2018

    • Author(s)
      岸信彦, 森田寛之, 田畑裕幸, 通山由美
    • Organizer
      第68回日本薬学会近畿支部大会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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