| Project/Area Number |
15K09454
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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) |
柏木 浩和 大阪大学, 医学系研究科, 講師 (10432535)
加藤 恒 大阪大学, 医学系研究科, 助教 (20705214)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | インテグリン / αIIbβ3 / 血小板 / CalDAG-GEFI / トロンビン受容体 / PAR4 / αIIbΒ3 / 多型 / Rap 1 / kindlin3 / Rap1 |
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| Outline of Final Research Achievements |
The objective of this project is to identify and characterize regulatory molecules that are involved in inside-out signaling for αIIbβ3 (αIIbβ3 activation) in detail. We identified a patient with CalDAG-GEFI deficiency (4th case in the world), and employing our velocity assay we revealed that markedly delayed αIIbβ3 activation in the proband. In addition, flow chamber experiments further revealed the impaired thrombus formation of the proband's platelets. We also investigate the association between PAR4 polymorphism and platelet activation including αIIbβ3 activation. As compared with PAR4Thr120, αIIbβ3 activation was more easily induced by PAR4-AP in platelets with PAR4Thr120. The Gq downstream ERK phosphorylation activity was associated with the difference in the platelet activation.
In this projects, we demonstrate roles of ClDAG-GEFI and PAR4 polymorphism on platelet function, especially αIIbβ3 activation.
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