Identification of the therapeutic target in the early phase of development of systemic sclerosis related organ involvement

• Project/Area Number: 16K09909
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: Nippon Medical School
• Principal Investigator: Shirai Yuichiro 日本医科大学, 医学部, 助教 (70528801)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 強皮症 / 血管病変 / 内科 / 線維化

Outline of Final Research Achievements

We aimed to investigate to identify the target protein at the early developing phase of organ involvement in patients of systemic sclerosis. Plasma PTX3 level was significantly increased in the order of stage of vascular involvement and highest in critical limb ischemia patients. Elevation of PTX3 level preceded the development of vascular involvement and subsequently the number of endothelial progenitor cells in peripheral circulation decreased resulting in elevation of angiogenic factors FGF2 level after development. It was suggested that PTX3 can be a biomarker in the early phrase of vascular involvement.

Academic Significance and Societal Importance of the Research Achievements

本研究ではPTX3が強皮症血管病変の最も初期から変動する分子の一つであることが明らかになった。強皮症血管病変は難治性であり、血管拡張薬を投与しても指肢切断を余儀なくされる場合も少なくない。その場合、本人のQOLだけでなく、医療費や介護負担など社会的コストもかかる。PTX3を標的とした治療法を開発することで、進展度を軽減できる可能性を秘めており、さらに血管生物学の進歩の一助にもなりうる。

Research Products

• [Presentation] Clinical characteristics of critical limb ischemia in systemic sclerosis (2018)
  • Author(s): Yuichiro Shirai, Yuka Okazaki, Masataka Kuwana
  • Organizer: 5th systemic sclerosis world congress
  • Int'l Joint Research