| Budget Amount *help |
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
Fiscal Year 2016: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Outline of Final Research Achievements |
The ductus arteriosus (DA) closes after birth to adapt to the robust changes in hemodynamics, which require intimal thickening to occur. The tissue-type plasminogen activator (t-PA) mRNA expression level was higher in DA endothelial cells (ECs) than in aortic ECs. t-PA-mediated marked gelatinase activity was observed at the site of disruption in the internal elastic laminae (IEL). In vivo administration of plasminogen to pre-term rat fetuses, in which intimal thickening is poorly formed, promoted IEL disruption accompanied by gelatinase activation, and enhanced intimal thickening formation in the DA. We also identified Fbln1 as a candidate gene for intimal thickening. Fibulin-1 is induced via plostaglandineE-EP4receptor signaling pathway in DA smooth muscle cells (SMCs). Fibulin-1 promoted SMC migration in combination with fibulin-1 binding protein versican. In conclusions, EC-derived t-PA and SMC-derived fibulin-1 promoted DA intimal thickening.
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