| Project/Area Number |
14570801
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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 | KANAZAWA UNIVERSITY |
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Principal Investigator |
TAKEHARA Kazuhiko Kanazawa University, School of Medicine, Professor, 大学院医学系研究科, 教授 (50142253)
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| Co-Investigator(Kenkyū-buntansha) |
SHIRASAKI Fumiaki Kanazawa University, School of Medicine, Assistant, 大学院医学系研究科, 助手 (10313644)
SATO Shinichi Kanazawa University, School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (20215792)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2003: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2002: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | TGF-β / CTGF / systemic sclerosis / fibrosis / transgenic mouse / TGFβ / コラーゲン / 動物モデル |
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| Research Abstract |
Systemic sclerosis(SSc)is a multisystem disorder of connective tissue characterized by excessive fibrosis in the skin and various internal organs such as lung, heart, kidney and esophagus.Trans forming growth factor(TGF-β)and connective tissue growth factor(CTGF)have received attention as an essential factor in pathogenesis of SSc.We established an animal model of skin fibrosis by TGF-β injection into subcutaneous tissue of newborn mice and investigated the role of CTGF in skin fibrosis.We utilized transgenic repoter mice harboring the -17kb promoter sequence of the mouse COL1A2 linked to either a firefly luciferase gene or a bacterial b-galactosidase gene.Serial injections of CTGF after TGF-β resulted in a sustained elevation of COL1A2 mRNA expression and promoter activity compared with consecutive injection of TGF-β alone on day 8.We also demonstrated that the number of fibroblasts with activated COL1A2 transcription was increased by serial injections of CTGF after TGF-β in comparison with injection of TGF-β alone.
These results suggested that CTGF maintains TGF-β-induced skin fibrosis by sustaining COL1A2 promoter activation and increasing the number of activated fibroblasts.
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