2010 Fiscal Year Final Research Report

Clock genes regulate circadian variation of blood pressure via Na-K-ATPase

Research Project

Project/Area Number	21790814
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Single-year Grants
Research Field	Kidney internal medicine
Research Institution	Hiroshima University
Principal Investigator	NAKASHIMA Ayumu Hiroshima University, 大学院・医歯薬学総合研究科, 助教 (40448262)
Project Period (FY)	2009 – 2010
Keywords	腎臓 / 尿細管 / 血管 / 血圧 / 時計遺伝子 / Na-K-ATPase
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.

(3 results)