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The role of Syk in the pathogenesis of systemic sclerosis

Research Project

Project/Area Number 26461680
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Dermatology
Research InstitutionKanazawa University

Principal Investigator

Takehara Kazuhiko  金沢大学, 医学系, 教授 (50142253)

Co-Investigator(Kenkyū-buntansha) 松下 貴史  金沢大学, 附属病院, 講師 (60432126)
Project Period (FY) 2014-04-01 – 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 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywords全身性強皮症 / B細胞 / Syk / 線維化
Outline of Final Research Achievements

Murine sclerodermatous chronic graft-versus-host disease (Scl-cGVHD) is a model for human Scl-cGVHD and systemic sclerosis (SSc). Syk is a protein tyrosine kinase that has an important role in transmitting signals from a variety of cell surface receptors.This study aims to investigate the effect of a Syk inhibitor, R788, on Scl-cGVHD and role of Syk in patients with SSc. Allogeneic BMT increased Syk phosphorylation in T, B, and CD11b+ cells. Early administration of Syk inhibitor attenuated severity and fibrosis of Scl-cGVHD. Syk inhibitor also reduced skin mRNA expressions of IL-13, IL-17A, and TGF-β1. However,Syk phosphorylation in B cell of SSc patients was not increased compared with that of normal control. The current studies suggested that Syk inhibitor is a potential candidate for use in treating patients with Scl-cGVHD and SSc.

Report

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

    (11 results)

All 2017 2016 2015 2014

All Journal Article (5 results) (of which Peer Reviewed: 5 results,  Acknowledgement Compliant: 3 results) Presentation (5 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (1 results)

  • [Journal Article] Blockade of p38 Mitogen-Activated Protein Kinase Inhibits Murine Sclerodermatous Chronic Graft-versus-Host Disease.2017

    • Author(s)
      Matsushita T, Date M, Kano M, Mizumaki K, Tennichi M, Kobayashi T, Hamaguchi Y, Hasegawa M, Fujimoto M, Takehara K.
    • Journal Title

      Am J Pathol

      Volume: 187 Issue: 4 Pages: 841-850

    • DOI

      10.1016/j.ajpath.2016.12.016

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Decreased Levels of Regulatory B cells in Patients with Systemic Sclerosis: Association with autoantibody production and disease activity.2016

    • Author(s)
      Matsushita T, Hamaguchi Y, Hasegawa M, Takehara K, Fujimoto M.
    • Journal Title

      Rheumatology (Oxford).

      Volume: 55 Issue: 2 Pages: 263-267

    • DOI

      10.1093/rheumatology/kev331

    • NAID

      120005764209

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Clinical and immunological predictors of scleroderma renal crisis in Japanese systemic sclerosis patients with anti-RNA polymerase III antibodies.2015

    • Author(s)
      Hamaguchi Y, Kodera M, Matsushita T, Usuda T, Kuwana M, Takehara K, and Fujimoto M
    • Journal Title

      Arthritis Rheumatol

      Volume: 67 Issue: 4 Pages: 1045-1052

    • DOI

      10.1002/art.38994

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 6.A crucial role of L-selectin in C protein-induced experimental polymyositis in mice.2014

    • Author(s)
      Oishi K, Hamaguchi Y, Matsushita T, Hasegawa M, Okiyama N, Dernedde J, Weinhart M, Haag R, Tedder TF, Takehara K, Kohsaka H, Fujimoto M.
    • Journal Title

      Arthritis Rheumatol.

      Volume: 66 Pages: 1864-71

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] 7.The clinical characteristics of juvenile-onset systemic sclerosis in Japanese patients.2014

    • Author(s)
      Hatta Y, Hasegawa M, Matsushita T, Hamaguchi Y, Fujimoto M, Takehara K.
    • Journal Title

      Mod Rheumatol.

      Volume: 24 Pages: 377-9

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Presentation] Current topics in systemic sclerosis2016

    • Author(s)
      Takehara K
    • Organizer
      Vietnamese Society of Dermatology & Venerelogy
    • Place of Presentation
      Vietnam
    • Year and Date
      2016-03-25
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 強皮症:最近の話題 全身性強皮症における制御性B細胞の役割2016

    • Author(s)
      松下貴史
    • Organizer
      第115回日本皮膚科学会総会
    • Place of Presentation
      京都
    • Related Report
      2016 Annual Research Report
  • [Presentation] Decreased Levels of Regulatory B cells in Patients with Systemic Sclerosis: Association witn autoantibody production2015

    • Author(s)
      Matsushita T, Hamaguchi Y, Hasegawa M, Fujimoto M, Takehara K
    • Organizer
      45th Annual ESDR Meeting
    • Place of Presentation
      オランダ
    • Year and Date
      2015-09-09
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗トポイソメラーゼⅠ抗体陽性の小児限局性強皮症の1例2015

    • Author(s)
      竹原和彦,清水恭子,松下貴史,濱口儒人
    • Organizer
      日本皮膚科学会新潟地方会
    • Place of Presentation
      新潟
    • Year and Date
      2015-04-05
    • Related Report
      2015 Research-status Report
  • [Presentation] Blockade of Syk Ameliorates the Development of Sclerodermatous Chronic Graft-Versus-Host Disease.2014

    • Author(s)
      Matsushita T, Le Huu D, Kimura H, Date M, Hamaguchi Y, Hasegawa M, Fujimoto M, Takehara K
    • Organizer
      ESDR 2014
    • Place of Presentation
      Copenhagen
    • Year and Date
      2014-09-11 – 2014-09-13
    • Related Report
      2014 Research-status Report
  • [Book] Systemi Sclerosis.2016

    • Author(s)
      Takehara K, Fujimoto M, Kuwana M
    • Total Pages
      247
    • Publisher
      Springer
    • Related Report
      2015 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2021-01-27  

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