2021 Fiscal Year Final Research Report
Development of new treatment for diabetic nephropathy using nanobiotechnology
| Project/Area Number |
19K17732
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Teikyo University (2020-2021)
The University of Tokyo (2019) |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 糖尿病性腎症 / ミネラルコルチコイド受容体 / MR / Rac1 / 高血圧 / アルドステロン |
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| Outline of Final Research Achievements |
Diabetic nephropathy (DN) is progressive and there is still no cure to adequately control its progression. The lack of model animals showing similar pathophysiological conditions to human DN is also a key factor in delaying drug development and its clinical application.
In this study, we established a new mouse of DN (UNx-HS db/db mice; uninephrectomy + high-salt loading to db/db mice). To evaluate the involvement of the Rac1-MR pathway in the DN progression, we investigated the effects of the MR antagonist, and the Rac1 inhibitor, on blood pressure and glomerular injury in UNx-HS db/db mice. UNx-HS db/db mice showed massive albuminuria accompanied by glomerular injury with nodular lesions, hypertension and hypokalemia. We further demonstrated that activation of Rac1-MR pathway in distal tubules and glomeruli is involved in DN progression through hypertension and glomerular injury, respectively.
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| Free Research Field |
腎臓内科学
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病性腎症は末期腎不全の原疾患として最多だが、基盤となる病態は未解明であり、病態解明ならびに治療薬開発は喫緊の課題である。本研究は遠位ネフロンおよび糸球体におけるRac1-MR経路活性化が、高血圧および糸球体障害を介した糖尿病性腎症進行に関与していることを指摘した。これは糖尿病性腎症治療の戦略としてRac1阻害薬とともにMR拮抗薬の有効性を示唆している。
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