THERAPEUTIC STRATEGY OF RHEUMATOID ARTHRITIS BY THE REGULATION OF ANTI-ONCOGENE p53 AND AN ANTI-ANGIOGENIC FACTOR.

2000 Fiscal Year Final Research Report Summary

• Project/Area Number: 11670460
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: 内科学一般
• Research Institution: TOKYO WOMEN'S MEDICAL UNIVERSITY
• Principal Investigator: YAMANAKA Hisashi TOKYO WOMEN'S MEDICAL UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (10166754)
• 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)
• Project Period (FY): 1999 – 2000
• Keywords: RHEUMATOID ARTHRITIS / ANGIOGENESIS / SYNOVITIS / THROMBOSPONDIN-1 / COLLAGEN-INDUCED ARTHRITIS

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.