| Project/Area Number |
26293404
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Conservative dentistry
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| Research Institution | Tohoku University |
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Principal Investigator |
Saito Masahiro 東北大学, 歯学研究科(研究院), 教授 (40215562)
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| Co-Investigator(Kenkyū-buntansha) |
福本 敏 東北大学, 歯学研究科(研究院), 教授 (30264253)
江草 宏 東北大学, 歯学研究科(研究院), 教授 (30379078)
山田 聡 大阪大学, 歯学部附属病院, 講師 (40359849)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2015: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2014: ¥9,620,000 (Direct Cost: ¥7,400,000、Indirect Cost: ¥2,220,000)
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| Keywords | マルファン症候群 / 結合組織疾患 / 細胞外マトリックス / 弾性線維 / 歯科疾患 / 生物製剤 / 解離性大動脈瘤 / 遺伝性疾患 / 歯学 / 再生医療 / トランスレーショナルリサーチ / バイオテクノロジー / 循環器 / 大動脈瘤 / 歯周病 / 創薬開発 / 分解酵素 / マウスモデル / 微細線維 |
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| Outline of Final Research Achievements |
Marfan syndrome (MFS) that is a severe, systemic disorder of connective tissue with predominant involvement of the ocular, cardiovascular and musculoskeltal system. Cardiovascular manifestations in the form of dissecting thoracic aortic aneurysms, mitral valve prolapse and myocardial dysfunction are the major cause of morbidity and mortality in MFS. The molecular pathogenesis of MFS proceeded principally through the activation of TGF-beta signaling and metalloproteinase expression have shown to cause as a common mechanisms that leads to aortic degeneration. Here we showed the novel mechanisms of ADAMTSL6beta on the accelerating ADAMTS4 activity to progress aortic aneurysm and dissection in MFS through versican degradation. Thus, our results suggest that recruitment of ADAMTS4 to fibrillin-1 microfibril by ADAMTSL6beta promotes versican degradation and that this axis may provide a new insight for pathogenesis of aortic aneurysm and dissection in MFS.
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