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Analysis of pathogenesis of systemic sclerosis based on dysfunctional endothelial progenitor cells and its application to novel therapeutic interventions

Research Project

Project/Area Number 19390275
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionKeio University

Principal Investigator

KUWANA Masataka  Keio University, 医学部, 准教授 (50245479)

Co-Investigator(Kenkyū-buntansha) SETA Noriyuki  慶應義塾大学, 医学部, 助教 (40338372)
SATOH Takashi  慶應義塾大学, 医学部, 助教 (90407114)
KANEKO Yuko  慶應義塾大学, 医学部, 助教 (60317112)
INOUE Yumiko  慶應義塾大学, 医学部, 助教 (60348638)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2008: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000)
Fiscal Year 2007: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Keywords強皮症 / 血管内皮前駆細胞 / 血管新生 / 脈管形成 / 線維化 / ケモカイン / 単球 / 血管再生 / 末梢循環障害
Research Abstract

本研究ではヒト血管内皮前駆細胞(EPC)として知られている循環血管内皮前駆細胞(CEP)と単球系EPCの強皮症病態との関連を追究した。強皮症患者ではCEPの減少と分化障害があり、それを代償するために動員されたMEPが局所のMCP-1濃度を高めることで線維化を促進する機序が明らかにされた。本研究成果によりEPCの機能異常が強皮症特有の血管病変と線維化病態の両者を誘導することが証明され、EPCを標的とした手法が強皮症に対する新たな治療となりえることが示された。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (22 results)

All 2009 2008 2007

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (13 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Estrogen receptor gene polymorphisms in Japanese patients with systemic sclerosis2008

    • Author(s)
      1. Hoshi M, Yasuoka H, Kuwana M.
    • Journal Title

      Clin. Exp. Rheumatol 26(5)

      Pages: 914-917

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] A CD40-CD154 interaction in tissue fibrosis2008

    • Author(s)
      Kawai M, Masuda A, Kuwana M.
    • Journal Title

      Arthritis Rheum 58(11)

      Pages: 3562-3573

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human circulating monocytes can express receptor activator of nuclear factor-αB ligand and differentiate into functional osteoclasts without exogenous stimulation2008

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

      Immunol. Cell Biol 86(5)

      Pages: 453-459

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Human circulating monocytes can express receptor activator of nuclear factor-kB ligand and differentiate into functional osteoclasts without exogenous stimulation2008

    • Author(s)
      Seta N, Okazaki Y, Kuwana M
    • Journal Title

      Immunology and Cell Biology 86

      Pages: 453-459

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A CD40-CD154 interaction in tissue fibrosis2008

    • Author(s)
      Kawai M, Masuda A, Kuwana M
    • Journal Title

      Arthritis & Rheumatism 58

      Pages: 3562-3573

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Estrogen receptor gene polymorphisms in Japanese patients with systemic sclerosis2008

    • Author(s)
      Hoshi M, Yasuoka H, Kuwana M
    • Journal Title

      Clinical Experimental Rheumatology 26

      Pages: 914-917

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Human circulating monocytes as multipotential progenitors2007

    • Author(s)
      Seta N, Kuwana M.
    • Journal Title

      Keio J. Med. 56(2)

      Pages: 41-47

    • NAID

      130000103945

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Presentation] 強皮症末梢血単球のフェノタイプ解析第12回強皮症研究会2009

    • Author(s)
      増田絢子、安岡秀剛、山口由衣、岡崎有佳、佐藤隆司、桑名正隆
    • Organizer
      第12回強皮症研究会
    • Place of Presentation
      東京
    • Year and Date
      2009-01-17
    • Related Report
      2008 Final Research Report
  • [Presentation] Fibrogenic gene expression profiles in circulating monocytes from patients with systemic sclerosis (SSc)2008

    • Author(s)
      増田絢子、安岡秀剛、山口由衣、佐藤隆司、桑名正隆
    • Organizer
      第38回日本免疫学会総会
    • Place of Presentation
      京都
    • Year and Date
      2008-12-03
    • Related Report
      2008 Final Research Report
  • [Presentation] Hepatocyte growth factor promoter gene polymorphism controls severity of interstitial lung disease in patients with systemic sclerosis2008

    • Author(s)
      Hoshino K, Satoh T, Kuwana M
    • Organizer
      The 72nd Annual Scientific Meeting of American College of Rheumatology
    • Place of Presentation
      San Francisco
    • Year and Date
      2008-10-27
    • Related Report
      2008 Final Research Report
  • [Presentation] Insufficient repair as a mechanism for scleroderma vasculopathy2008

    • Author(s)
      Kuwana M
    • Organizer
      13th Congress of the Asia Pacific League of Associations for Rheumatology
    • Place of Presentation
      Yokohama
    • Year and Date
      2008-09-24
    • Related Report
      2008 Annual Research Report 2008 Final Research Report
  • [Presentation] Circulating endothelial cell progenitors in scleroderma2008

    • Author(s)
      Kuwana M
    • Organizer
      The 10th International Workshop for Scleroderma Research
    • Place of Presentation
      Cambridge
    • Year and Date
      2008-08-05
    • Related Report
      2008 Final Research Report
  • [Presentation] 強皮症におけるHGF及びその受容体の一塩基多型解析2008

    • Author(s)
      星野香菜、佐藤隆司、桑名正隆
    • Organizer
      第52回日本リウマチ学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2008-04-22
    • Related Report
      2008 Final Research Report
  • [Presentation] 強皮症末梢血単球のフェノタイプ解析2008

    • Author(s)
      増田絢子、山口由衣、岡崎有佳、佐藤隆司、桑名正隆
    • Organizer
      第52回日本リウマチ学会総会
    • Place of Presentation
      札幌
    • Year and Date
      2008-04-22
    • Related Report
      2008 Final Research Report
  • [Presentation] 強皮症における単球系血管内皮前駆細胞(MEP)の解析2008

    • Author(s)
      桑名正隆、山口由衣、増田絢子、岡崎有佳、高橋一夫、池澤善郎
    • Organizer
      第11回強皮症研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-01-19
    • Related Report
      2008 Final Research Report
  • [Presentation] 強皮症におけるHGFおよびその受容体の一塩基多型(SNP)解析2008

    • Author(s)
      星野香菜、佐藤隆司、桑名正隆
    • Organizer
      第11回強皮症研究会
    • Place of Presentation
      東京
    • Year and Date
      2008-01-19
    • Related Report
      2008 Final Research Report
  • [Presentation] Paradoxical increase in monocytic progenitors for endothelial cells in patients with systemic sclerosis2007

    • Author(s)
      Yamaguchi Y, Okazaki Y, Seta N, Satoh T, Takahashi K, Ikezawa Z, Kuwana M
    • Organizer
      The 71th Annual Scientific Meeting of American College of Rheumatology
    • Place of Presentation
      Boston
    • Year and Date
      2007-11-08
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] Deficient vascular repair as a mechanism for scleroderma vascular disease2007

    • Author(s)
      Kuwana M
    • Organizer
      Carwile LeRoy Memorial International Workshop on Scleroderma(Professor E.)
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-05-19
    • Related Report
      2008 Final Research Report
  • [Presentation] A critical role of the CD40-CD154 interaction in fibroblast activation2007

    • Author(s)
      Kuwana M, Kawai M, Furuya Y
    • Organizer
      Carwile LeRoy Memorial International Workshop on Scleroderma(Professor E.)
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-05-18
    • Related Report
      2008 Final Research Report
  • [Presentation] Hepatocyte growth factor gene polymorphism can predict end-stage lung disease in patients with systemic sclerosis2007

    • Author(s)
      Hoshino K, Satoh T, Kuwana M
    • Organizer
      Carwile LeRoy Memorial International Workshop on Scleroderma(Professor E.)
    • Place of Presentation
      Tokyo
    • Year and Date
      2007-05-18
    • Related Report
      2008 Final Research Report
  • [Patent(Industrial Property Rights)] 単球由来多能性細胞(MOMC)の効率的な作製法2007

    • Inventor(s)
      桑名正隆、加藤尚志、瀬田範行、宮崎洋
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Filing Date
      2007-10-23
    • Related Report
      2008 Final Research Report
  • [Patent(Industrial Property Rights)] 単球由来多能性細胞(MOMC)の効率的な作製法2007

    • Inventor(s)
      桑名 正隆、加藤 尚志、瀬田 範行、宮崎 洋
    • Industrial Property Rights Holder
      学校法人慶應義塾
    • Filing Date
      2007-10-23
    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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