The efficacy of RAGE-DNA aptamer for prevention of hypertensive nephropathy
| Project/Area Number |
16K08564
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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 |
General pharmacology
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| Research Institution | Kurume University |
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Principal Investigator |
Shibata Ryo 久留米大学, 医学部, 講師 (10723588)
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| Co-Investigator(Kenkyū-buntansha) |
深水 圭 久留米大学, 医学部, 教授 (80309781)
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| Research Collaborator |
TAGUCHI kensei
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 高血圧性腎障害 / RAGE / 終末糖化産物 / ミネラロコルチコイド受容体 / RAGEアプタマー / 慢性腎臓病 / RAGE-DNAアプタマ- / アルドステロン / RAGE-DNAアプタマー / 核酸アプタマー / 鉱質コルチコイド受容体 / カルボキシメチルリジン |
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| Outline of Final Research Achievements |
Hypertension-induced kidney disease (HKD) is one of the major diseases that are linked to progression of chronic kidney disease (CKD); however, there has been few sovereign remedies to prevent onset and progression of HKD. Therefore, it is necessary to create new therapeutic strategy for slowing down progression of HKD. Our data demonstrated that mineralocorticoid receptor, a main contributor for CKD progression, is activated by advanced glycation endproducts through receptor for AGE (RAGE). We created DNA aptamer directed against RAGE which functions as antagonist of RAGE and found that RAGE-DNA aptamer is capable of inhibiting progression of HKD through inactivation of MR and subsequently inhibition of profibrotic process. These findings suggest that AGE-RAGE axis is involved in HKD progression and RAGE-DNA aptamer is potentially new therapeutic strategy for inhibition of HKD onset and progression.
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| Academic Significance and Societal Importance of the Research Achievements |
我々はAGE-RAGE系の活性化が血圧とは独立してミネラロコルチコイド受容体活性化を介して慢性腎臓病の発症進展に関与していることを発見した。この知見は、AGE-RAGE系が高齢者で活性化していることから鑑みて、高齢者高血圧症症例において血圧を厳密に管理しても高血圧性腎障害を改善できないというクリニカルクエッションを解明するヒントであると考えている。さらに我々はRAGEに対するアンタゴニストとして機能するDNAアプタマーを共同研究で開発し、それが高血圧マウスにおいて腎障害を抑制することを突き止めた。以上よりRAGEに対するDNAアプタマーが高血圧性腎障害に対する新たな治療戦略になる可能性がある。
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Report
(4 results)
Research Products
(5 results)
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[Journal Article] RAGE-aptamer Blocks the Development and Progression of Experimental Diabetic Nephropathy.2017
Author(s)
Matsui, T., Higashimoto, Y., Nishino, Y., Nakamura, N., Fukami, K., Yamagishi, S.
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Journal Title
Diabetes
Volume: 66
Issue: 1
Pages: 1683-1695
DOI
NAID
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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