| Project/Area Number |
25461249
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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 |
Kidney internal medicine
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
UMEMURA Satoshi 横浜市立大学, 医学系研究科, 教授 (00128589)
谷津 圭介 横浜市立大学, 大学病院, 助教 (10457856)
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| Co-Investigator(Renkei-kenkyūsha) |
YATSU Keisuke 横浜市立大学, 附属病院, 助教 (10457856)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | ATP2B1 / hypertension / nitric oxide / GWAS / mice / knock out / 高血圧 / 血管平滑筋 / 尿細管 / ノックアウト / トランスジェニック / PMCA1 / 一酸化窒素 / 細胞内カルシウム / カルシウム利尿 / eNOS |
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| Outline of Final Research Achievements |
In the ‘Millennium Genome Project’, we identified ATP2B1 as a gene responsible for hypertension through GWAS. However the role of the ATP2B1 gene in blood pressure homeostasis have not yet determined. Thus, we generated systemic heterozygous ATP2B1 null(ATP2B1+/-) mice. ATP2B1+/- mice revealed significantly higher SBP by a radio telemetric method. Phenylephrine-induced vasoconstriction was significantly increased in vascular rings from ATP2B1+/- mice, and the difference in this contraction disappeared in the presence of a nitric oxide synthase (NOS) inhibitor. In cultured endothelial cells from ATP2B1+/- mice, the phosphorylation (Ser-1177) level of NOS protein had decreased, and the production of nitric oxide was lower compared to those of control mice. These results suggest that decreased ATP2B1 gene expression is associated with impaired endothelial NOS activity and nitric oxide production, and the ATP2B1 gene plays a crucial role in the regulation of blood pressure.
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