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Development of novel strategies for treating systemic sclerosis focusing on circulating monocytes

Research Project

Project/Area Number 26461471
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Collagenous pathology/Allergology
Research InstitutionNippon Medical School

Principal Investigator

KUWANA Masataka  日本医科大学, 大学院医学研究科, 教授 (50245479)

Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords強皮症 / 単球 / マクロファージ / 肺高血圧症 / 肺線維症 / 動物モデル
Outline of Final Research Achievements

Systemic sclerosis or scleroderma is characterized by excessive fibrosis of the skin and other internal organs, and still remains an intractable condition based on lack of any effective therapeutics. In this study, we have found that macrophages are recruited to the affected organs before development of apparent fibrosis in a mouse model for systemic sclerosis. Macrophages detected in the affected organs are primarily fibrogenic M2 macrophages, which are upregulated under a control of transcription factor Fra-1. Gene expression of Fra-1 is also increased in circulating monocytes derived from patients with systemic sclerosis, compared with those from healthy controls. In summary, our results together indicate that upregulated expression of Fra-1 promotes differentiation of monocytes into M2 macrophages, which are recruited to the skin and other organs affected and promote excessive fibrosis.

Report

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

    (23 results)

All 2016 2015 2014 Other

All Journal Article (14 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 9 results,  Acknowledgement Compliant: 8 results,  Open Access: 1 results) Presentation (8 results) (of which Int'l Joint Research: 6 results) Remarks (1 results)

  • [Journal Article] Elevated serum Krebs von den Lungen-6 in early disease predicts subsequent deterioration of pulmonary function in patients with systemic sclerosis and interstitial lung disease2016

    • Author(s)
      Kuwana M, Shirai Y, and Takeuchi T
    • Journal Title

      J. Rheumatol.

      Volume: 43 Pages: 1835-1831

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Recent updates in experimental protocols for endothelial cells.2016

    • Author(s)
      Kahaleh B, Guiducci S, and Kuwana M
    • Journal Title

      J. Scleroderma Rel. Dis

      Volume: 1 Pages: 257-265

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 単球由来多能性細胞を用いた膠原病治療の可能性を探る2016

    • Author(s)
      桑名正隆
    • Journal Title

      分子リウマチ治療

      Volume: 258 Pages: 19-23

    • Related Report
      2016 Annual Research 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] Rapid initiation of intravenous epoprostenol infusion is the favored option in patients with advanced pulmonary arterial hypertension2015

    • Author(s)
      Kimura M, Tamura Y, Takei M, Yamamoto T, One T, Kuwana M, Fukuda K, and Satoh T
    • Journal Title

      PLoS One

      Volume: 10 Issue: 4 Pages: e0121894-e0121894

    • DOI

      10.1371/journal.pone.0121894

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Oral vasopressin receptor antagonist tolvaptan in right heart failure due to pulmonary hypertension2015

    • Author(s)
      Tamura Y, Kimura M, Takei M, Ono T, Kuwana M, Satoh T, Fukuda K, and Humbert M
    • Journal Title

      Eur. Respir. J

      Volume: 46 Issue: 1 Pages: 283-286

    • DOI

      10.1183/09031936.00044915

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 強皮症の新たな治療概念2015

    • Author(s)
      桑名正隆
    • Journal Title

      臨床リウマチ

      Volume: 27 Pages: 281-287

    • NAID

      130005141285

    • Related Report
      2015 Research-status Report
  • [Journal Article] 強皮症重症例に対する治療2015

    • Author(s)
      桑名正隆
    • Journal Title

      分子リウマチ治療

      Volume: 8 Pages: 50-53

    • Related Report
      2015 Research-status Report
  • [Journal Article] 強皮症性混合型肺高血圧症に対する病態評価と治療のポイント2015

    • Author(s)
      桑名正隆
    • Journal Title

      内科

      Volume: 117 Pages: 449-454

    • Related Report
      2015 Research-status Report
  • [Journal Article] Elevated pentraxin 3 in systemic sclerosis: associations with vascular manifestations and defective vasculogenesis.2015

    • Author(s)
      Shirai Y, Okazaki Y, Inoue Y, Tamura Y, Yasuoka H, Takeuchi T, and Kuwana M.
    • Journal Title

      Arthritis Rheumatol

      Volume: 67 Issue: 2 Pages: 498-507

    • DOI

      10.1002/art.38953

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 免疫抑制薬の臨床応用実践論2015

    • Author(s)
      桑名正隆
    • Journal Title

      炎症と免疫

      Volume: 23 Pages: 90-95

    • Related Report
      2014 Research-status Report
  • [Journal Article] Autoantibodies to RuvBL1 and RuvBL2: a novel systemic sclerosis-related antibody associated with diffuse cutaneous and skeletal muscle involvement.2014

    • Author(s)
      Kaji K, Fertig N, Medsger TA Jr, Satoh T, Hoshino K, Hamaguchi Y, Hasegawa M, Lucas M, Schnure A, Ogawa F, Sato S, Takehara K, Fujimoto M, Kuwana M.
    • Journal Title

      Arthritis Care Res

      Volume: 66 Issue: 4 Pages: 575-84

    • DOI

      10.1002/acr.22163

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Impaired in vivo neovascularization capacity of endothelial progenitor cells in patients with systemic sclerosis.2014

    • Author(s)
      Kuwana M, and Okazaki Y.
    • Journal Title

      Arthritis Rheumatol

      Volume: 66 Issue: 5 Pages: 1300-1305

    • DOI

      10.1002/art.38326

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] 強皮症の病態と最新治療2014

    • Author(s)
      桑名正隆
    • Journal Title

      Medicina

      Volume: 51 Pages: 2409-2413

    • Related Report
      2014 Research-status Report
  • [Presentation] An Increased Circulating Level of Periostin in Patients with Systemic Sclerosis: Associations with Functional Impairment in Various Affected Organs Display combined fields only if separate fields don't exist2016

    • Author(s)
      Yamaguchi Y, Shirai Y, Ono J, Kawaguchi Y, Izuhara K, Kuwana M and Aihara M
    • Organizer
      80th Annual Scientific Meeting of American College of Rheumatology
    • Place of Presentation
      Washington, DC
    • Year and Date
      2016-11-11
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Predictors of digital ulcer in SSc: endothelial progenitor cells and circulating biomarkers.2016

    • Author(s)
      Kuwana M
    • Organizer
      18th Asia Pacific League of Associations for Rheumatology Congress.
    • Place of Presentation
      Shanghai
    • Year and Date
      2016-09-28
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] M2-Shifted Mice Recapitulate Dermal and Pulmonary Remodeling2016

    • Author(s)
      Yasuoka H, Tam Y. Y, Okazaki Y, Tamura Y, Matsuo K, Takeuchi T, Kuwana M
    • Organizer
      4th Systemic Sclerosis World Congress
    • Place of Presentation
      Lisbon/PORTUGAL
    • Year and Date
      2016-02-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Efficacy and Safety of Tocilizumab in Patients with Systemic Sclerosis: Experiences in a Routine Clinical Setting2016

    • Author(s)
      Shirai Y, Takeuchi T, Kuwana M
    • Organizer
      4th Systemic Sclerosis World Congress
    • Place of Presentation
      Lisbon/PORTUGAL
    • Year and Date
      2016-02-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Parameters That Predict Worsening of Skin Thickness in Patients with Early Diffuse Cutaneous Systemic Sclerosis2015

    • Author(s)
      Kuwana M, Hasegawa, M Shirai Y, Ishikawa O, Endo H, Ogawa F, Goto D, Sato S, Ihn H, Kawaguchi Y and Takehara K
    • Organizer
      79th Annual Scientific Meeting of American College of Rheumatology
    • Place of Presentation
      San Francisco/USA
    • Year and Date
      2015-11-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Clinical Utility of Serial KL-6 Measurement in Interstitial Lung Disease Associated with Systemic Sclerosis2015

    • Author(s)
      Shirai Y, Takeuchi T and Kuwana M
    • Organizer
      79th Annual Scientific Meeting of American College of Rheumatology
    • Place of Presentation
      San Francisco/USA
    • Year and Date
      2015-11-06
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] 強皮症に対するIL-6阻害療法2015

    • Author(s)
      桑名正隆
    • Organizer
      第59回日本リウマチ学会総会
    • Place of Presentation
      名古屋/日本
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report
  • [Presentation] Elevated Pentraxin 3 in Patients with Systemic Sclerosis: Associations with Vascular Manifestations and Defective Vasculogenesis.2014

    • Author(s)
      Shirai Y, Okazaki Y, Inoue Y, Tamura Y, Yasuoka H, Takeuchi T, and Kuwana M
    • Organizer
      The 78th Annual Scientific Meeting of American College of Rheumatology
    • Place of Presentation
      Boston/USA
    • Year and Date
      2014-11-14 – 2014-11-19
    • Related Report
      2014 Research-status Report
  • [Remarks] 日本医科大学大学院医学研究科 アレルギー膠原病内科【業績の紹介】

    • URL

      http://www.nms-rheum.jp

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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