2007 Fiscal Year Final Research Report Summary
Analysis of the pathogenesis and the treatment for scleroderma by using HGF-plasmid
| Project/Area Number |
17591162
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Dermatology
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| Research Institution | Tokyo Medical and Dental University |
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Principal Investigator |
NISHIOKA Kiyoshi Tokyo Medical and Dental University, Dermatology, Professor emeritus (20077647)
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| 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)
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| Project Period (FY) |
2005 – 2007
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| Keywords | Scleroderma / TGF-b / HGF / Chemokine / Cytokine / Gene therapy / Protease |
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| 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.
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