| Project/Area Number |
12470176
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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, Department of Dermatology, Professor, 大学院・医歯学総合研究科, 教授 (20077647)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Toshiyuki Tokyo Medical and Dental Univesity, Department of Dermatology, Lecturer, 医学部附属病院, 講師 (30242192)
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| Project Period (FY) |
2000 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥4,200,000 (Direct Cost: ¥4,200,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2001: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Scleroderma / Bleomycin / TGF-β / Animal model / 強皮症 / ブレオマイシン / 動物モデル / サイトカイン / 線維芽細胞 |
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| Research Abstract |
We previously established a mouse model for scleroderma by repeated local injections of bleomycin (J Invest Dermatol 1999 ; 112 : 456-462, J Rheumatol 1999 ; 26 : 2628-2634, Arch Dermatol Res 2000 ; 292 : 535-541). In this model, systemic treatment of interferon-γ reduced the development of dermal sclerosis (Arch Dermatol Res 2000 ; 292 : 362-365), whereas halofuginone was not effective (Rheumatology 2002 ; 41 : 594-596). Dermal sclerosis was also induced by bleomycin treatment in SCID mice, suggesting bleomycin-induced scleroderma is T cell independent (J Invest Dermatol 2001 ; 117 : 999-1001). Furthermore, expression of collagen was upregulated in mast cell-deficient mice (Arch Dermatol Res 2001 ; 293 : 532-536). Sclerotic fibroblasts following bleomycin treatment changed the phenotype into myofibroblasts, which were positive for α-smooth muscle actin (α-SMA), and neutralizing anti-TGF-β antibody decreased the number of α-SMA positive fibroblasts. Comparative study among various strains of mice revealed that increased expression and production of TGF-β in the lesional skin of bleomycin-'susceptible' strains.
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