| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
The regulation of platelet activation is quite important for prevention of arterial thrombosis. To explore the mechanism of platelet activation, the intraplatelet signaling was analyzed in platelets of patients with macrothrombocytopenia. Increased FAK phosphorylation in all of the platelets with integrin αIIb cytoplasmic tail mutations suggests the importance ofαIIb cytoplasmic tail in platelet signaling. The effect of mutation in αIIb cytoplasmic tail was also studied using αIIb-(R995W) knock-in mice. The number of platelets, platelet production, and the surface expression of αIIbβ3 were decreased in knock-in mice. Furthermore, in vitro thrombus formation under flow condition was significantly impaired in knock-in mice. The analysis of a patient with bleeding problems due to CalDAG-GEFI deficiency clearly showed the role of CalDAG-GEFI in αIIbβ3 inside-out signaling. These results will contribute for better anti-platelet therapy in patients with arterial thrombosis.
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