2020 Fiscal Year Final Research Report
Regulation of Cardiovascular and Metabolic Diseases by RAGE-Aptamer - Study in Animal Models
| Project/Area Number |
19K16387
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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 47040:Pharmacology-related
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| Research Institution | Kurume University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2021-03-31
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| Keywords | 終末糖化産物受容体 / 2型糖尿病 / アプタマー |
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| Outline of Final Research Achievements |
Interaction of advanced glycation end products (AGEs) with the receptor RAGE plays a role in the development and enhancement of diabetic complications.
We examined whether RAGE-aptamer inhibited tubular damage in KKAy/Ta mice, obese type 2 diabatic mice with insulin resistance. Eight-week-old KKAy/Ta mice received continuous intraperitoneal infusion of RAGE-aptamer for 4- or 8-weeks. RAGE-aptamer significantly inhibited the increase in urinary NAG activity and HOMA-IR in diabetic mice. Furthermore, renal AGE, RAGE, and NADPH oxidase activity were significantly decreased in RAGE-aptamer-treated mice, while adipose tissue adiponectin expression was increased with amelioration of histological alterations in glomerular and interstitial area.
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| Free Research Field |
生化学
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病患者数は増加の一途を辿っており，予備軍を含め2200万人が糖尿病合併症のリスクにさらされている。糖尿病腎症は新規透析導入の原因疾患第一位であり，年間1万6千人が新たに透析導入に至るほどの社会問題となっている。
本研究においてRAGEアプタマーの投与が糖尿病マウスの腎尿細管障害およびインスリン抵抗性を改善したことから，腎臓および脂肪組織のAGE－RAGE系の阻害が腎症およびインスリン抵抗性の新規治療標的となりうることが期待される。
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