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Analysis of the pathogenesis and the treatment for scleroderma by using HGF-plasmid

Research Project

Project/Area Number 17591162
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Dermatology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

NISHIOKA Kiyoshi  Tokyo Medical and Dental University, Dermatology, Professor emeritus (20077647)

Co-Investigator(Kenkyū-buntansha) YOKOZEKI Hiroo  Tokyo Medical and Dental University, Dermatology, Professor (90210608)
YAMAMOTO Toshiyuki  Tokyo Medical and Dental University, Dermatology, Assistant Professor (30242192)
佐藤 貴浩  東京医科歯科大学, 大学院医歯学総合研究科, 助教授 (30235361)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,450,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥150,000)
Fiscal Year 2007: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsScleroderma / TGF-b / HGF / Chemokine / Cytokine / Gene therapy / Protease / TGF-β / モデルマウス / 膠原病 / 肺線維症
Research Abstract

Systemic sclerosis (SSc) is a connective tissue disorder with an unknown etiology. There are currently no effective therapies for SSc. In this study, working with a bleomycine (BLM)-induced scleroderma model mice, we performed two transfections of human HGF cDNA into the skeletal muscle and showed that this treatment not only helped to prevent the dermal sclerosis simultaneously injected BLM but also improved the symptoms of dermal sclerosis induced by ELM 4 weeks previously. RT-PCR, ELISA and an immunohistochemical analysis revealed that both mRNA and protein of human HGF as well as murine HGF were enhanced in the skin, lung, muscle and the serum after two transfections of human HGF cDNA. These analyses also revealed that this treatment significantly reduced both the expression of the TGF-β1 mRNA and the production of TGF-β1 on macrophage-like cells which infiltrated the dermis and the fibroblastic cells in BLM-induced scleroderma. Furthermore, HGF gene transfection both prevented and ameliorated the symptoms of not only dermal sclerosis but also of lung fibrosis induced by a subcutaneous ELM injection. These results indicated that gene therapy by the transfection of the human HGF cDNA may thus be a useful therapy for SSc and lung fibrosis involved with SSc. Further, we tried to apply Smad3,4 decoy ODN for the treatment of BLM-indued scleroderma. Smad decoy ODN also inhibited the sclerosis in duced by BML.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (24 results)

All 2007 2006 2005

All Journal Article (20 results) (of which Peer Reviewed: 5 results) Presentation (2 results) Book (2 results)

  • [Journal Article] Fas-and FasL-deficient mice are resistant to the induction of bleomycin-induced scleroderma.2007

    • Author(s)
      Yamamoto T, Yokozeki H, Nishioka K.
    • Journal Title

      Arch Dermatol Res 298(9)

      Pages: 465-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Odontogenic focal infection could be partly involved in the pathogenesis of atopic dermatitis as exacerbating factor.2007

    • Author(s)
      Igawa K, Nishioka K. Yokozeki H.
    • Journal Title

      Int J Dermatol 46(4)

      Pages: 376-379

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Airborne contact dermatitis due to Japanese cedar pollen.2007

    • Author(s)
      Yokozeki H, Satoh T, Katayama l, Nishioka K.
    • Journal Title

      Contact Dermatitis 56(4)

      Pages: 224-8

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Fas- and FasL-deficient mice are resistant to the induction of bleomycin-induced scleroderma2007

    • Author(s)
      Yamamoto T, Yokozeki H, Nishioka K.
    • Journal Title

      Arch Dermatol Res 298(9)

      Pages: 465-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Odontogenic focal infection could be partly involved in the pathogenesis of atopic dermatitis as exacerbating factor2007

    • Author(s)
      Igawa K, Nishioka K, Yokozeki H.
    • Journal Title

      Int J Dermatol 46(4)

      Pages: 376-9

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Airborne contact dermatitis due to Japanese cedar pollen2007

    • Author(s)
      Yokozeki H, Satoh T, Katayama I, Nishioka K.
    • Journal Title

      Contact Dermatitis 56(4)

      Pages: 224-8

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Odontogenic focal infection could be partly involved in the pathogenesis of atopic dermatitis as exacerbating factor.2007

    • Author(s)
      Igawa K, Nishioka K, Yokozeki H.
    • Journal Title

      Int J Dermatol 46(4)

      Pages: 376-379

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Airborne contact dermatitis due to Japanese cedar pollen.2007

    • Author(s)
      Yokozeki H, Satoh T, Katayama I, Nishioka K.
    • Journal Title

      Contact Dermatitis, 56(4)

      Pages: 224-8

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Fas- and FasL-deficient mice are resistant to the induction of bleomycin-induced scleroderma.2006

    • Author(s)
      Yamamoto T, Yokozeki H, Nishioka K
    • Journal Title

      Arch Dermatol Res. 298(9)

      Pages: 465-8

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Prostaglandin D2 plays an essential role in chronic allergic inflammation of the skin via CRTH2 receptor.2006

    • Author(s)
      Satoh T, Moroi R, et al.
    • Journal Title

      J Immunol. 15;177(4)

      Pages: 2621-9

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Reduction of human T-cell leukemia virus type 1 (HTLV-1) proviral loads in rats orally infected with HTLV-1 by reimmunization with HTLV-1-infected cells.2006

    • Author(s)
      Komori K, et al.
    • Journal Title

      J Virol. 80(15)

      Pages: 7375-81

    • Related Report
      2006 Annual Research Report
  • [Journal Article] STAT-6-mediated control of P-selectin by substance P and interleukin-4 in human dermal endothelial cells.2006

    • Author(s)
      Miyazaki Y, Satoh T, Nishioka K, Yokozeki H.
    • Journal Title

      Am J Pathol. 169(2)

      Pages: 697-707

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Flagellate erythema2006

    • Author(s)
      Yamamoto T, Nishioka K
    • Journal Title

      Int J Dermatol 45(5)

      Pages: 627-31

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Yellow nails under bucillamine therapy for rheumatoid arthritis : a report of two cases.2006

    • Author(s)
      Yamamoto T, Yokozeki H
    • Journal Title

      Pheumatol Int Nov 14

      Pages: 1437-1437

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Increased expression of p53 and p21 (waf1/Cip1) in lesional skin of bleomycin-induced scleroderma.2005

    • Author(s)
      Yamamoto T, Nishioka K
    • Journal Title

      Arch Dermatol Res 296(11)

      Pages: 509-513

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Plasminogen activator inhibitor-1 is elevated, but not essential, in the development of bleomycin-induced murine scleroderma.2005

    • Author(s)
      Matsushita M, Yamamoto T, Nishioka K
    • Journal Title

      Clin Exp Immunol 39

      Pages: 429-438

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Humanized anti-interleukin-6 receptor antibody treatment of multicentric Castleman disease.2005

    • Author(s)
      Nishimoto N, Kanakura Y, Nishioka K, Kishimoto T et al.
    • Journal Title

      Blood 106(8)

      Pages: 2627-2632

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Synthesis of α (1,3) fucosyltransferases IV-and VII-dependent eosinophil selectin ligand and recruitment to the skin.2005

    • Author(s)
      Satoh T, Kanai Y, Wu M-H, Yokozeki H, Nishioka K et al.
    • Journal Title

      Am J Pathol 167(3)

      Pages: 787-796

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Basophils play a critical role in the development of IgE-mediated chronic allergic inflammation independently of T cells and mast cells.2005

    • Author(s)
      Mukai K, Matsuoka K, Taya C, Suzuki Yokozeki H, Nishioka K
    • Journal Title

      Immunity; 23(3)

      Pages: 191-202

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Multiple cutaneous fibrous histiocytoma in association with systemic lupus erythematosus.2005

    • Author(s)
      Yamamoto T, Sumi K, Yokozeki H, Nishioka K
    • Journal Title

      J Dermatol 32

      Pages: 645-649

    • NAID

      10020270944

    • Related Report
      2005 Annual Research Report
  • [Presentation] Cutaneous manifestations of Oriental patients with dermatomyositis and the seborrheic pattern of facial eryhtema2007

    • Author(s)
      H. Yokozeki, N. Okiyama, et. al.
    • Organizer
      21th World Congress
    • Place of Presentation
      Buenos Aires
    • Year and Date
      2007-10-01
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Cutaneous manifestations of Oriental patie nts with dermatomyositis and the seborrheic pattern of facial eryhtema2007

    • Author(s)
      H. Yokozeki, N. Okiyama, et. al.
    • Organizer
      21th World Congress
    • Place of Presentation
      Buenos Ai res
    • Year and Date
      2007-10-01
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 蕁麻疹 ガイドライン:外来診療20072007

    • Author(s)
      横関博雄
    • Publisher
      医薬ジャーナル社
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 今日の治療指針20072007

    • Author(s)
      横関博雄
    • Total Pages
      1668
    • Publisher
      医学書院
    • Related Report
      2006 Annual Research Report

URL: 

Published: 2005-04-01   Modified: 2016-04-21  

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