| Project/Area Number |
15K09420
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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 |
Endocrinology
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| Research Institution | Tohoku University |
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Principal Investigator |
Hakoda Akiko 東北大学, 医学系研究科, 大学院非常勤講師 (70509398)
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| Co-Investigator(Kenkyū-buntansha) |
菅原 明 東北大学, 医学系研究科, 教授 (90270834)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | アルドステロン / 高血圧 / レチノイド / RXR / CYP11B2 |
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| Outline of Final Research Achievements |
PA024 dose-dependently suppressed AII-induced CYP11B2 mRNA expression/promoter activity. Additionally, high-dose PA024 significantly decreased aldosterone secretion. The suppression of CYP11B2 promoter activity by PA024 was observed in the deletion mutants analyses using the region from -1521 (full length) to -135 including NBRE-1, Ad4, and Ad5 elements. PA024 also suppressed mRNA expression of transcription factors Nurr1 and NGFIB in a dose-dependent manner. Since PA024-mediated suppression of CYP11B2 promoter activity was rescued by Nurr1 overexpression, decrease of Nurr1 expression may contribute to the suppression. PA024 also inhibited mRNA expression of StAR, HSD3β2, and CYP21A2. Therefore, PA024-mediated suppression of these enzymes may also be involved in the inhibition of aldosterone synthesis. Furthermore, PA024 significantly lowered systemic blood pressure in THM.
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