| Project/Area Number |
23591567
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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 |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
KOGAKI Shigetoyo 大阪大学, 医学(系)研究科(研究院), 講師 (00311754)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Kunihiko 大阪大学, 医学(系)研究科(研究院), 特任助教(常勤) (10610230)
ICHIMORI Hiroaki 大阪大学, 医学部附属病院, 医員 (60467553)
NAWA Nobutoshi 大阪大学, 医学部附属病院, 医員 (30617543)
ISHIDA Hidekazu 大阪大学, 医学部附属病院, 医員 (50467552)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 肺高血圧症 / CNP / ナトリウム利尿ペプチド受容体 / cGMP / PAH |
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| Research Abstract |
Recently, we have reported a novel missense mutation in the NPR-B gene (2647G>A; Val 883 Met) in a family case showing overgrowth and bone anomalies.We have found that overexpression of the mutated protein in human pulmonary artery smooth muscle cells (PASMCs) induced significant increase in cGMP levels compared to WT-NPR-B or GFP control in a ligand-independent manner. Overexpression of Mut-NPR-B suppressed proliferation in PASMCs. In vivo, rats treated with the combination of SU5416 and hypoxia developed pulmonary hypertension, right ventricular hypertrophy and pulmonary vascular obstructive lesions. Intratracheal administration of adenoviral vectors carrying Mut-NPR-B resulted in tendency toward an improvement in vascular remodeling as measured by medial wall thickness of pulmonary vessels compared to WT-NPR-B or GFP control
(GFP, 52+-13%; WT-NPR-B, 50+-4%; Mut-NPR-B, 44+-2 %, n=4).
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