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2018 Fiscal Year Final Research Report

The efficacy of RAGE-DNA aptamer for prevention of hypertensive nephropathy

Research Project

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Project/Area Number 16K08564
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General pharmacology
Research InstitutionKurume University

Principal Investigator

Shibata Ryo  久留米大学, 医学部, 講師 (10723588)

Co-Investigator(Kenkyū-buntansha) 深水 圭  久留米大学, 医学部, 教授 (80309781)
Research Collaborator TAGUCHI kensei  
Project Period (FY) 2016-04-01 – 2019-03-31
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
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.

Free Research Field

高血圧性腎障害

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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Published: 2020-03-30  

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