| Project/Area Number |
17K10770
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Cardiovascular surgery
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| Research Institution | Kurume University |
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Principal Investigator |
FURUSHO AYA 久留米大学, 医学部, 助教 (80597427)
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| Co-Investigator(Kenkyū-buntansha) |
青木 浩樹 久留米大学, 付置研究所, 教授 (60322244)
田中 啓之 久留米大学, 医学部, 教授 (70197466)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 大動脈解離 / 免疫グロブリン / Syk / B細胞 |
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| Outline of Final Research Achievements |
We examined the role of Syk in pathogenesis of arctic dissection (AD) using human AD tissue and mouse model of AD. Immunohistochemical staining of human AD tissue revealed that B cells were enriched at the entry site of AD. B cell infiltration and Syk activation were observed in mouse model of AD. Unexpectedly, administration of Syk inhibitor worsened AD, indicating the protective role of Syk. In B cell-deficient muMT mouse, BAPN+AngII induced significantly less severe AD compared to wild type. Depositions of IgG and fibrinogen, one of the endogenous antigen for natural IgG, were observed after BAPN+AngII infusion before and after AD development in wild type mice. Deposition of fiblinogen was also observed in muMT mice after BAPN+AngII infusion. Infusion of IgG to muMT worsened AD. Therefore, Syk is protective against AD, while B cells and IgG promote AD. Our findings may provide the conceptual foundation of the diagnostic and therapeutic strategies for AD.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、大動脈解離におけるB細胞および免疫制御分子Sykの役割を解明することを目的とした。解離病態ではSykが組織保護的に作用し、IgGが組織破壊を統合的に制御する可能性を見出した。IgGの作用は多面性があるが、主に炎症促進と炎症抑制に大別される。今後、IgGの作用を個別に検討することで、解離病態における組織破壊と組織保護のインバランスを制御するメカニズムが明らかになると期待される。近年、IgGの抑制型Fcγ受容体の作用を増強し免疫抑制シグナルを導入する創薬が開発されつつあり、本研究の成果から解離病態の組織破壊に対する抑制療法の開発が可能になると考えられる。
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