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The role of coagulation and complement systems in the pathogenesis of CSU

Research Project

Project/Area Number 21K08301
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 53050:Dermatology-related
Research InstitutionHiroshima University

Principal Investigator

Yanase Yuhki  広島大学, 医系科学研究科(薬), 准教授 (40452586)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2023: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2022: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2021: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords慢性蕁麻疹 / 血液凝固 / 補体 / マイクロパーティクル / マスト細胞 / 好塩基球
Outline of Research at the Start

慢性蕁麻疹の発症機序は、何らかの刺激を受けた皮膚マスト細胞や好塩基球から放出されるヒスタミン等が、皮膚微小血管や知覚神経に作用して、かゆみを伴う膨疹を形成すると考えられている。しかし、慢性蕁麻疹において、皮膚マスト細胞や末梢血好塩基球を活性化する機構は未だ明らかでない。また、慢性蕁麻疹の程度を客観的に評価するマーカーも確立されていない。そこで本申請では、慢性蕁麻疹の病態における血液凝固系・補体系の役割に着目し、血液凝固系を指標とした慢性蕁麻疹の新しい評価法の確立と、血液凝固因子と補体が皮膚マスト細胞・好塩基球を活性化して膨疹を形成する機序を解明する。

Outline of Final Research Achievements

Chronic spontaneous urticaria (CSU) is characterized by daily or almost daily recurring wheal and flare with itch for more than 6 weeks. The extrinsic coagulation system has been shown to be activated in correlation with CSU severity. However, detailed relationship between the pathogenesis of CSU and coagulation system has not been clear. We here clarified that tissue factor (TF), a trigger of the extrinsic coagulation cascade, expressed on vascular endothelial cells plays critical roles in CSU and activated complement, C5a, are also important for basophils and mast cells activation in CSU. Moreover, we demonstrated that micro particles (MP) released from vascular endothelial cells have important roles in the pathogenesis of CSU.

Academic Significance and Societal Importance of the Research Achievements

本研究では、慢性蕁麻疹の病態と、血液凝固反応・補体系の関係の一部を解明し、また、血液内物質が慢性蕁麻疹の診断に応用できる可能性を示した。本成果は、難治性慢性蕁麻疹の新しい治療薬の開発と診断法の開発につながるものと期待する。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (14 results)

All 2023 2022 2021

All Journal Article (8 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 7 results,  Open Access: 6 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 4 results)

  • [Journal Article] Basophil Characteristics as a Marker of the Pathogenesis of Chronic Spontaneous Urticaria in Relation to the Coagulation and Complement Systems2023

    • Author(s)
      Yanase Yuhki、Matsubara Daiki、Takahagi Shunsuke、Tanaka Akio、Ozawa Koichiro、Hide Michihiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 12 Pages: 10320-10320

    • DOI

      10.3390/ijms241210320

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Time Course of Priming Effect of TF Inducers on Synergistic TF Expression and Intra-Cellular Gap Formation of Human Vascular Endothelial Cells via the Extrinsic Coagulation Cascade2023

    • Author(s)
      Matsubara Daiki、Kunieda Takuma、Yanase Yuhki、Takahagi Shunsuke、Uchida Kazue、Kawaguchi Tomoko、Ishii Kaori、Tanaka Akio、Ozawa Koichiro、Hide Michihiro
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 15 Pages: 12388-12388

    • DOI

      10.3390/ijms241512388

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Immunological Changes of Basophil Hyperreactivity to Sweat in Patients With Well-Controlled Atopic Dermatitis2022

    • Author(s)
      Numata Tomofumi、Takahagi Shunsuke、Ishii Kaori、Morioke Satoshi、Kan Takanobu、Mizuno Hayato、Yanase Yuhki、Kawaguchi Tomoko、Tanaka Akio、Hide Michihiro
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 883605-883605

    • DOI

      10.3389/fimmu.2022.883605

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Basophils activation of patients with chronic spontaneous urticaria in response to C5a despite failure to respond to IgE-mediated stimuli2022

    • Author(s)
      Matsubara Daiki、Yanase Yuhki、Ishii Kaori、Takahagi Shunsuke、Tanaka Akio、Ozawa Koichiro、Hide Michihiro
    • Journal Title

      Frontiers in Immunology

      Volume: 13 Pages: 994823-994823

    • DOI

      10.3389/fimmu.2022.994823

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Homocysteine causes neuronal leptin resistance and endoplasmic reticulum stress2022

    • Author(s)
      Preninka Arini Isnani、Kuriya Karen、Yazawa Kyosuke、Yoshii Michiko、Yanase Yuhki、Jockers Ralf、Dam Julie、Hosoi Toru、Ozawa Koichiro
    • Journal Title

      PLOS ONE

      Volume: 17 Issue: 12 Pages: e0278965-e0278965

    • DOI

      10.1371/journal.pone.0278965

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Living-cell analysis by surface plasmon resonance and its medical application.2021

    • Author(s)
      Yanase Y, Hide M.
    • Journal Title

      Biomedical Engineering.

      Volume: 1

    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Journal Article] The Pathogenesis of Chronic Spontaneous Urticaria: The Role of Infiltrating Cells2021

    • Author(s)
      Gimenez-Arnau Ana M.、de Montjoye Laurence、Asero Riccardo、Cugno Massimo、Kulthanan Kanokvalai、Yanase Yuhki、Hide Michihiro、Kaplan Allen P.
    • Journal Title

      The Journal of Allergy and Clinical Immunology: In Practice

      Volume: 9 Issue: 6 Pages: 2195-2208

    • DOI

      10.1016/j.jaip.2021.03.033

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The Role of Coagulation and Complement Factors for Mast Cell Activation in the Pathogenesis of Chronic Spontaneous Urticaria2021

    • Author(s)
      Yanase Yuhki、Takahagi Shunsuke、Ozawa Koichiro、Hide Michihiro
    • Journal Title

      Cells

      Volume: 10 Issue: 7 Pages: 1759-1759

    • DOI

      10.3390/cells10071759

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 慢性蕁麻疹における組織因子発現細胞・マイクロパーティクルの機能解明と診断への応用2023

    • Author(s)
      柳瀬雄輝
    • Organizer
      第72回日本アレルギー学会学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] 慢性特発性蕁麻疹の病態における凝・補体系の役割2023

    • Author(s)
      柳瀬雄輝
    • Organizer
      第87回日本皮膚科学会東京支部学術大会
    • Related Report
      2023 Annual Research Report
    • Invited
  • [Presentation] ヒト血管内皮細胞における相乗的組織因子発現に対する組織因子誘発物質の時間解析2023

    • Author(s)
      國枝 拓真、柳瀬 雄輝、松原 大樹、高萩 俊輔、小澤 光一郎、秀 道広
    • Organizer
      第97回日本薬理学会年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] 慢性特発性蕁麻疹における血液凝固系と補体系の関係2022

    • Author(s)
      柳瀬雄輝
    • Organizer
      第71回日本アレルギー学会学術大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] 基礎・臨床研究から解明する慢性特発性蕁麻疹の病態2022

    • Author(s)
      柳瀬雄輝
    • Organizer
      第52回日本皮膚免疫アレルギー学会学術大会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] Complement component 5 produced by coagulation factors induces histamine release from human skin mast cells and peripheral basophils2021

    • Author(s)
      Yuhki Yanase, Yoshimi Matsuo, Tomoko Kawaguchi, Kaori Ishii, Koichiro Ozawa, Shunske Takahagi, Michihiro Hide.
    • Organizer
      GA2LEN UCARE Urticaria Conference 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research

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Published: 2021-04-28   Modified: 2025-01-30  

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