2010 Fiscal Year Final Research Report
Clock genes regulate circadian variation of blood pressure via Na-K-ATPase
| Project/Area Number |
21790814
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Kidney internal medicine
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| Research Institution | Hiroshima University |
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Principal Investigator |
NAKASHIMA Ayumu Hiroshima University, 大学院・医歯薬学総合研究科, 助教 (40448262)
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| Project Period (FY) |
2009 – 2010
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| Keywords | 腎臓 / 尿細管 / 血管 / 血圧 / 時計遺伝子 / Na-K-ATPase |
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| Research Abstract |
To identify target genes of DEC1, we utilized genome-wide chromatin immunoprecipitation (ChIP)-on-chip assay and found that DEC1 bound to the regulatory region of one of Na/K-ATPase genes. ChIP and luciferase reporter assays revealed that an E-box on the Na/K-ATPase gene promoter is a functional element governed by clock components. Since Na/K-ATPases are involved in the blood pressure regulation, we focused on a functional role of DEC1 in homeostasis and circadian regulation of blood pressure. In both kidney and aorta, robust circadian rhythms of the Na/K-ATPase expression were observed at mRNA and protein levels. DEC1-/- mice showed higher expression of Na/K-ATPase than wild type mice. In addition, DEC1-/- mice showed lower blood pressure than wild-type mice. In contrast, CLOCK mutant mice showed a lower expression level of Na/K-ATPase and higher blood pressure. We conclude that DEC1 regulates circadian variation of blood pressure via Na/K-ATPase gene expression.
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