A study of unction of an extracellular matrix molecule which could modulate pathophysiology of Kawasaki Disease.
| Project/Area Number |
16H05351
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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 |
Pediatrics
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| Research Institution | Mie University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大熊 喜彰 国立研究開発法人国立国際医療研究センター, その他部局等, 小児科医師 (10609168)
勝部 康弘 日本医科大学, 医学部, 准教授 (20246523)
三谷 義英 三重大学, 医学部附属病院, 准教授 (60273380)
高橋 啓 東邦大学, 医学部, 教授 (80216712)
俵 功 三重大学, 医学部附属病院, 講師 (80378380)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2016: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 炎症 / 動物モデル / バイオマーカー / 川崎病 / テネイシン / 細胞外マトリックス |
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| Outline of Final Research Achievements |
Kawasaki disease (KD) is an acute febrile illness of childhood characterized by systemic vasculitis and hyperendemic in Japan. The most critical complication is coronary aneurysm, however the pathophysiology remains unsolved. We studied the molecular function of a matricellular protein, tenascin-C(TN-C), in pathophysiology of KD and evaluated its potential for a diagnostic marker. In combined analysis with two kinds of experimental KD models using genetically engineered mice, human autopsy specimens and laboratory test on blood sample from the patients, we have found vascular smooth muscle cells and mesenchymal cells in adventitia in the vascular lesion synthesize TN-C stimulated by proinflammatory cytokines, which in turn, aggravates inflammation by activating macrophages. Furthermore, the elevated serum TN-C reflects disease activity and can be a predictive marker for high risk of coronary aneurysm formation and used to evaluate the effectiveness of the therapy.
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| Academic Significance and Societal Importance of the Research Achievements |
川崎病に合併する冠動脈瘤は、免疫グロブリン治療の普及により発症頻度こそ減少したが、今なお、根本的な治療法はもとより、その形成を予知する診断法も確立されていない重篤な病態である。従って、分子病態解明を基盤とした新しいバイオマーカーおよび分子治療標的治療法の開発が急務である。本研究では、細胞外マトリックス分子の一つtenascin-C(TN-C)が治療抵抗性、及び冠動脈瘤形成を予知し治療法を選択するための有用なマーカーとなることが明らかになった。さらに、TN-Cが炎症を増強する病態増悪因子として働きうること及びその作用機構の一端が明らかになっため、それを利用した新たな治療法の開発が期待される。
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Report
(4 results)
Research Products
(20 results)
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[Journal Article] Tenascin-C accelerates adverse ventricular remodelling after myocardial infarction by modulating macrophage polarization.2019
Author(s)
Kimura T., Tajiri K., Sato A., Sakai S., Wang Z., Yoshida T., Uede T., Hiroe M., Aonuma K., Ieda M., Imanaka-Yoshida K.
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Journal Title
Cardiovasc Res
Volume: 115
Pages: 614-624
Related Report
Peer Reviewed
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[Journal Article] Serum Tenascin-C as a Novel Predictor for Risk of Coronary Artery Lesion and Resistance to Intravenous Immunoglobulin in Kawasaki Disease – A Multicenter Retrospective Study –2016
Author(s)
Okuma Y., Suda K., Nakaoka H., Katsube Y., Mitani Y., Yoshikane Y., Ichida F., Matsushita T., Shichino H., Shiraishi I., Abe J., Hiroe M., Yoshida T., Imanaka-Yoshida K.
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Journal Title
Circulation Journal
Volume: 80
Issue: 11
Pages: 2376-2381
DOI
NAID
ISSN
1346-9843, 1347-4820
Related Report
Peer Reviewed
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