| Project/Area Number |
11670460
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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 |
内科学一般
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| Research Institution | TOKYO WOMEN'S MEDICAL UNIVERSITY |
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Principal Investigator |
YAMANAKA Hisashi TOKYO WOMEN'S MEDICAL UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (10166754)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAJIMA Hiroshi TOKYO WOMEN'S MEDICAL UNIVERSITY, ASSISTANT, 医学部, 助手 (40266838)
SENDO Wako TOKYO WOMEN'S MEDICAL UNIVERSITY, ASSISTANT, 医学部, 助手 (40277140)
TAIGUCHI Atsuo TOKYO WOMEN'S MEDICAL UNIVERSITY, ASSISTANT PROFESSOR, 医学部, 講師 (40179833)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | RHEUMATOID ARTHRITIS / ANGIOGENESIS / SYNOVITIS / THROMBOSPONDIN-1 / COLLAGEN-INDUCED ARTHRITIS / TSP-1 |
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| Research Abstract |
Angiogenesis is a characteristic feature in the synovitis in patients with early rheumatoid arthritis (RA), and also is believed to have a crucial role in the proliferation of rheumatoid synovium. Angiogenesis is balanced between the pro-angiogenic factors and anti-angiogenic factors. To elucidate the pathogenesis of angiogenesis in rheumatoid arthritis, we investigated the expression of pro-angiogenic factors including vascular endothelial growth factor (VEGF) and anti-angiogenjc factor, thrombospondin-1 (TSP-1). And we showed that the expression of TSP-1 is suppressed in synovial tissue with active inflammation, and this lead to an imbalance of pro-angiogenic factors and anti-angiogenic factors. From this notion, the regulation of factors involved in the angiogenesis is a candidate of molecular target in RA therapy, especially in patients with early RA.Thus, we investigated the introduction of TSP-1 gene in the experimental arthritis model mouse. In the preventive experiments, pre-introduction of TSP-1 plasmid into mouse with collagen-induced arthritis significantly delayed the onset of arthritis. Also, introduction of TSP-1 plasmid into the mouse who have already have collagen-induced arthritis suppressed the extent of arthritis. These results showed the suppression of angiogenesis by the over-expression of TSP-1 successfully inhibit the progression of synovitis. These investigations clearly showed the potential of TSP-1 introduction as a new strategy in RA treatment.
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