2018 Fiscal Year Final Research Report
Analysis of platelet integrin signaling and association with vascular diseases
| Project/Area Number |
16K09826
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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 |
Hematology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
冨山 佳昭 大阪大学, 医学部附属病院, 准教授 (80252667)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Keywords | インテグリン |
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| Outline of Final Research Achievements |
We identified CalDAG-GEFI deficiency and kindlin-3 deficiency by analysis of patients with severe bleeding tendency from their infancy. Using our developed αIIbβ3 activation kinetic assay, we revealed that delayed activation of αIIbβ3 leads to severe bleeding tendency.
Furthermore, we analyzed constitutive active αIIb(R995W) knock-in mice, and found that the mice showed macrothrombocytopenia like human subjects. We found that impaired proplatelet formation may responsible for the phenotype. KI mice also showed highly impaired platelet function mainly due to reduced αIIbβ3 expression in platelets.
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| Free Research Field |
血栓・止血学
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| Academic Significance and Societal Importance of the Research Achievements |
血小板は動脈硬化性血管病変の形成に中心的役割を担う。今回の研究により血小板機能の中で最も重要であるαIIbβ3の活性化に必須の分子とそのメカニズムの一端を明らかにした。またαIIbβ3の恒常的活性化が血小板産生の障害および血小板機能に重大な影響を与えることをマウスモデルを用いて明らかにした。これらによりαIIbβ3活性化の生体内における新たな生理的意義を明らかにするとともに、αIIbβ3活性化を制御する抗血小板薬開発の可能性を示した。
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