Identification and characterization of integrin inside-out signaling molecules employing a newly developed expeimental system
| 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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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Immature platelet fraction (IPF) as a apredictive value for thrombopoietic recovery after allogeneic stem cell transplantation2018
Author(s)
Sakuragi M, Hayashi S, Maruyama M, Kiyokawa T, Nagamine K, Fujita J, Maeda T, Kato H, Kashiwagi H, Kanakura Y, Tomiyama Y.
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Journal Title
International Journal of Hematology
Volume: 107
Issue: 3
Pages: 320-326
DOI
Related Report
Peer Reviewed
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[Journal Article] Expression levels of ABCG2 on cord red blood cells and study of fetal anemia associated with anti-Jr(a).2016
Author(s)
Fujita S, Kashiwagi H, Tomimatsu T, Ito S, Mimura K, Kanagawa T, Endo M, Miyoshi T, Okamura Y, Tani Y, Tomiyama Y, Kimura T.
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Journal Title
Transfusion.
Volume: 56
Issue: 5
Pages: 1171-1181
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Trans-fatty acid promotes thrombus formation in mice by aggravating antithrombogenic endothelial functions via Toll-like receptors.2014
Author(s)
Kondo K, Ishida T, Yasuda T, Nakajima H, Mori K, Tanaka N, Mori T, Monguchi T, Shinohara M, Irino Y, Toh R, Rikitake Y, Kiyomizu K, Tomiyama Y, Yamamoto J, Hirata K.
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Journal Title
Molecular Nutrition & Food Research
Volume: 59
Issue: 4
Pages: 729-740
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Complete failure of integrin aIIbb3 activation in kinetic assay associates with severe bleeding tendency in a patient with Kindlin-3 deficiency.2017
Author(s)
Kato H, Ito Y, Kashiwagi H, Morikawa Y, Akuta K, Nishiura N, Honda S, Kokame K, Miyata T, Kanakura Y, Tomiyama Y.
Organizer
International Society on Thrombosis and Haemostasis (ISTH) 2017 Congress
Related Report
Int'l Joint Research
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[Presentation] Pathophysiology and diagnosis of ITP2016
Author(s)
Tomiyama Y
Organizer
The 9th Congress of the Asian-Pacific Society on Thrombosis and Hemostasis
Place of Presentation
Taipei International Convention Center, Taiwan
Year and Date
2016-10-07
Related Report
Int'l Joint Research / Invited
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