2015 Fiscal Year Final Research Report
Contribution of novel MR cofactor CASZ1 to onset of hypertension
| Project/Area Number |
25461254
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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 | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 高血圧 |
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| Outline of Final Research Achievements |
Mineralocorticoid receptor belongs to the nuclear hormone receptor superfamily and serves as an aldosterone-induced transcriptional factor. However, molecular mechanism mediated through MR is barely known. To address this issue, we tried to identify novel MR co-regulators using HEK293 cells by a biochemical approach with LC-MS/MS analysis. A novel protein CASZ1 interacted with MR in vivo and was co-localized with MR in rat renal tubule. To address physiological significance of CASZ1, we generated renal tubule specific Casz1 knockout mouse. These mouse showed hypertensive phenotype compared with control（sBP cont. 115±3.8 VS cKO 135±3.3 mmHg:p<0.01）under DOCA+salt loading. Urinary potassium excretion was also increased compared with control (K/Cr ratio cont. 5.959±1.390 VS cKO 9.72±0.499:p<0.05). These data suggested activation of aldosterone action in the knockout mouse. In conclusion, CASZ1 is a novel MR co-repressor and plays important role in pathophysiology of hypertension.
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| Free Research Field |
高血圧
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