Analysis of regulatory mechanism of sustained integrin alphaIIbbeta3 activation.
| Project/Area Number |
26461403
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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 |
Kato Hisashi 大阪大学, 医学系研究科, 助教 (20705214)
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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)
冨山 佳昭 大阪大学, 医学部附属病院, 准教授 (80252667)
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| Co-Investigator(Renkei-kenkyūsha) |
Tomiyama Yoshiaki 大阪大学, 医学部附属病院・輸血部, 准教授 (80252667)
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| Research Collaborator |
Ichii Michiko 大阪大学, 大学院医学系研究科・血液・腫瘍内科, 寄付講座助教 (30633010)
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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 |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | インテグリンαIIbβ3 / Inside-Outシグナル / CalDAG-GEFI / 血小板 / インテグリン活性化 / 血栓 / inside-outシグナル |
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| Outline of Final Research Achievements |
Platelet fibrinogen receptor integrin αIIbβ3 is essential for hemostasis and its activation state is tightly regulated by inside-out signaling. So far, the detailed mechanism how inside-out signaling induces activation of αIIbβ3 is still obscure. In this study, we determined the molecules which are important for inside-out signaling in the megakaryocytic cell line CMK and the patient with CalDAG-GEFI deficiency who has been suffering severe bleeding problems. However, platelets with CalDAG-GEFI deficiency showed mildly impaired αIIbβ3 activation. And we found the delayed αIIbβ3 activation in CalDAG-GEFI deficient platelets is related to severe bleeding symptoms. Our results indicate the importance of CalDAG-GEFI and αIIbβ3 activation kinetics for normal hemostasis (Blood 2016).
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Report
(4 results)
Research Products
(14 results)
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[Presentation] Clinical significance of IPF% or RP% measurement in distinguishing primary immune thrombocytopenia from aplastic thrombocytopenic disorders.2015
Author(s)
SakuragiM, Hayashi S, Maruyama M, Kabutomori O, Kiyokawa T, Nagamine K, Kato H, Kashiwagi H, Kanakura Y, Tomiyama Y.
Organizer
The 25th Congress of the International Society on Thrombosis and Haemostasis.
Place of Presentation
Toronto, Canada
Year and Date
2015-06-24
Related Report
Int'l Joint Research
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[Presentation] alphaIIb（R990W), a constitutive activation mutation of integrin alphaIIbbeta3, kock-in mice show macrothrombocytopenia with impairment of platelet function.2014
Author(s)
Kiyomizu K, Kashiwagi H, Kunishima S, Banno F, Kato H, Morikawa Y, Tadokoro S, Kokame K, Honds S, Miyata T, Kanakura Y, Tomiyama Y
Organizer
The American Society of Hematology 56th annual meeting
Place of Presentation
San Francisco, USA
Year and Date
2014-12-08
Related Report
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