| Project/Area Number |
20K22908
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0902:General internal medicine and related fields
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| Research Institution | Yokohama City University |
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Principal Investigator |
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| Project Period (FY) |
2020-09-11 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2021: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 高血圧 / 皮膚組織 / レニン・アンジオテンシン系 / ナトリウム / ATRAP / レニン-アンジオテンシン系 / 皮膚 |
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| Outline of Research at the Start |
本研究では，「皮膚組織レニン‐アンジオテンシン系（RAS）が血圧・体液・電解質バランスの調節に寄与し，高血圧症の発症・進展に関わっている」との仮説を検証するため，1型アンジオテンシンII受容体（AT1受容体）情報伝達系の内在性抑制因子であるATRAP（AT1 receptor-associated protein）に着目し，病態モデル動物，皮膚組織特異的ATRAP発現制御動物，ヒト皮膚組織を用いて，高血圧症における皮膚組織RASの病態生理学的意義の解明を目指す．
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| Outline of Final Research Achievements |
Hypertension is the most powerful risk factor for the development of cardiovascular diseases. Yet, its pathophysiology has not been fully elucidated. In this current study, we intended to investigate the pathophysiological significance of skin tissue renin-angiotensin system (RAS) in the development of hypertension with focusing on angiotensin II (Ang II) type 1 receptor (AT1R)-associated protein (ATRAP) that is an endogenous suppressor for the AT1R signal transduction. 129/Sv mice have been reported that its systemic RAS activity is upregulated compared to C57BL/6 mice. Compared to C57BL/6 mice, 129/Sv mice exhibited an exacerbation of Ang II-dependent hypertension mice along with a tendency of increasing skin sodium amount. On the other hand, this tendency in skin sodium amount was not found when these mice were received high-salt loading despite an exacerbated hypertension in 129/Sv mice. In addition, we have already generated keratinocyte-specific ATRAP knock-out mice.
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| Academic Significance and Societal Importance of the Research Achievements |
高血圧は心血管病の最大の危険因子であるにもかかわらず，その病態生理は十分に解明されていない．本研究により，皮膚組織が高血圧発症の新たなプレイヤーとして機能している可能性，またそのメカニズムとして皮膚組織レニン・アンジオテンシン系が関与している可能性が示された．今後，皮膚組織RASを標的にした高血圧の新規治療法の開発にもつながる可能性を有しており，その学術的・社会的意義は大きい．
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