2021 Fiscal Year Final Research Report
Potential novel antihypertensive therapy through BubR1 gene transfer for Hypertension
| Project/Area Number |
19K09249
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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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| Review Section |
Basic Section 55030:Cardiovascular surgery-related
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| Research Institution | National Hospital Organization, Fukuoka Higashi Medical Center (Department of clinical research) (2021)
Kyushu University (2020)
International University of Health and Welfare (2019) |
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Principal Investigator |
Matsumoto Takuya 独立行政法人国立病院機構福岡東医療センター(臨床研究部), 独立行政法人国立病院機構福岡東医療センター臨床研究部, 血管外科医長 (20374168)
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| Co-Investigator(Kenkyū-buntansha) |
古山 正 九州大学, 大学病院, 講師 (00419590)
森崎 浩一 九州大学, 大学病院, 助教 (30625801)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 高血圧 / BubR1 / 老化 / 細胞周期遺伝子 / レニン・アンジオテンシン |
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| Outline of Final Research Achievements |
A systemic mild BubR1 reduction repressed Ang II‐induced hypertension by attenuating AGTR1 overexpression in the kidneys. The hypotensive effect of BubR1 reduction in RPTCs occurred through a repression of the upregulations of AGTR1 and Nox4. Renal‐specific BubR1 reduction may be a promising new therapy for preventing the development of hypertension and AGTR1 overexpression in the kidneys by acting as an AGTR1 blocker. This would be useful not only as an antihypertensive therapy but potentially also as a means of protecting heart and kidney functions. Further studies are required to clarify the relationship between BubR1 and the Ang II-AGTR1 pathway.Ang II-induced hypertension is caused by AGTR1 overexpression in the kidneys via the upregulation of BubR1 and Nox4.
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| Free Research Field |
血管外科
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| Academic Significance and Societal Importance of the Research Achievements |
全身性にBubR1発現を軽度低下させると、Ang II刺激による腎臓でのAGTR1過剰発現が抑制され、血圧上昇が軽減された。腎近位尿細管細胞におけるBubR1低発現の降圧効果は、AGTR1やNox 4の過剰発現の抑制によるものである。腎特異的なBubR1発現低下は、AGTR1拮抗作用によって、高血圧発症や腎臓でのAGTR1過剰発現を抑制する新規治療方法となり得る。この治療法は、降圧療法として有用なだけでなく、潜在的な心腎機能保護にもなり得る。AngⅡ誘導性の血圧上昇は、BubR1とNox4発現の上昇を介した腎臓におけるAGTR1の過剰発現によって引き起こされている。
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