| Project/Area Number |
18K16006
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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 | Keio University |
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Principal Investigator |
Azegami Tatsuhiko 慶應義塾大学, 保健管理センター(日吉), 助教 (60573376)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 糖尿病性腎臓病 / 腎臓 / ワクチン / 糖尿病 / 終末糖化産物 / 糖尿病性腎症 |
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| Outline of Final Research Achievements |
Effective treatment of diabetic kidney disease (DKD) remains a large unmet medical need. Advanced glycation end-products (AGEs) - receptor for AGEs (RAGE) axis plays a pivotal role in the development and progression of DKD. To provide a new therapeutic strategy against DKD progression, we developed a vaccine against RAGE. The immunization of mice with the RAGE vaccine induced antigen-specific serum IgG antibody titers and attenuated the increase in urinary albumin excretion in streptozotocin (STZ)-induced diabetic mice (type 1 diabetes model) and leptin-receptor deficient db/db mice (type 2 diabetes model). In microscopic analyses, RAGE vaccination suppressed glomerular hypertrophy and mesangial expansion in both diabetic models and significantly reduced glomerular basement membrane thickness in STZ-induced diabetic mice. Thus, our newly developed RAGE vaccine attenuated the progression of DKD in mice and is a promising potential therapeutic strategy for patients with DKD.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病では慢性の経過で血管合併症が発症・進展するため、長期の治療・管理が必要となる。本邦の糖尿病有病者は約1,000万人と推定され、患者数は膨大である。腎症は、血管合併症の1つで、末期腎不全のリスクであり、透析療法導入における原疾患として最多である。さらに、心血管疾患の発症リスクを増大し、糖尿病患者の生命予後に寄与する。したがって、糖尿性腎症の治療戦略を確立することは、(1) 患者個々の心血管予後・生命予後を改善、(2) 末期腎不全への進展を抑制、(3) 末期腎不全治療にかかる莫大な費用を抑制につながるため、本研究にて、腎症の進展抑制に寄与しうる新規戦略を開発できたことは社会的に意義が高い。
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