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KAKEN_18K16006seika.pdf
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糖尿病性腎症に対する新規治療戦略の開発
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トウニョウビョウセイ ジンショウ ニ タイスル シンキ チリョウ センリャク ノ カイハツ
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Tōnyōbyōsei jinshō ni taisuru shinki chiryō senryaku no kaihatsu
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The development of new therapeutic strategy for diabetic nephropathy
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畔上, 達彦
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アゼガミ, タツヒコ
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Azegami, Tatsuhiko
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慶應義塾大学・保健管理センター (日吉) ・助教
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Research team head
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科研費研究者番号 : 60573376
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2021
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科学研究費補助金研究成果報告書
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2020
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糖尿病性腎臓病(DKD)はアンメット・メディカル・ニーズの高い疾患で、その発症・進展には終末糖化産物受容体(RAGE)が深く関与する。DKDに対する治療戦略を構築するため、RAGEを標的とした治療ワクチンを開発した。RAGEワクチン接種により、ストレプトゾトシン投与マウス(1型糖尿病モデル)とレプチン受容体欠失db/dbマウス(2型糖尿病モデル)で、尿中アルブミン排泄,糸球体腫大,メサンギウム基質拡大,糸球体基底膜肥厚が軽減された。これらの結果から、我々の開発したRAGEワクチンは、DKDの進展抑制に有効であり、今後、DKD患者に対する新たな治療戦略となる可能性が示唆された。
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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研究種目 : 若手研究
研究期間 : 2018~2020
課題番号 : 18K16006
研究分野 : 腎臓内科
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