Suppressive effects of pyrrole-imidazole polyamides targeting TGF-beta1 as novel biomedicines on the diabetic nephropathy
| Project/Area Number |
17K09716
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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 |
Kidney internal medicine
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| Research Institution | Nihon University |
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Principal Investigator |
ABE Masanori 日本大学, 医学部, 教授 (70459890)
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| Co-Investigator(Kenkyū-buntansha) |
松本 宜明 日本大学, 薬学部, 教授 (10199896)
福田 昇 日本大学, 総合科学研究所, 教授 (40267050)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 糖尿病性腎症 / TGF-β1 / USF1 / PIポリアミド / 糖尿病腎症 / ポドサイト / 間質線維化 |
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| Outline of Final Research Achievements |
In the current study, we developed pyrrole-imidazole polyamides on the diabetic nephropathy. The cultured renal mesangial cells (MCs) showed proliferation with increases in expression of TGF-β1, which was suppressed with PI polyamide targeting rat TGF-β1. In in vivo experiments, streptozotosine-induced diabetic nephropaty in rats showed 1) epithelial-mesenchimal transition (EMT), 2) endothelial-mesenchymal transition (EndMT) of glomerular endothelium, 3) podocyte injury. Intraperitoneal administration of PI polyamide targeting rat TGF-β1 improve the EMT, the EndMT and the podocyte injury in diabetic nephropathy in rats. Moreover, we designed and synthesized PI polyamide preventing binding of transcription factor USF-1 in TGF-β1 promoter inhibited increased expression of TGF-β1 that increased in MCs with high glucose condition.
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| Academic Significance and Societal Importance of the Research Achievements |
ピロール・イミダゾール(PI)ポリアミドは中分子ペプチド化合物で次世代の薬として期待されている。今回、分子設計、合成しTGF-β1 PIポリアミド、 USF-1 PIポリアミドが糖尿病腎症を改善したことは、糖尿病腎症の進展悪化にTGF-β1とUSF-1が関与している事が分かり、今後の創薬に対し学術的意義は大きい。またTGF-β1 やUSF-1 PIポリアミドが次回、霊長類サル類に糖尿病腎症を作成し、その効果を観、効果が確認されれば最終的にAMED、製薬会社との共同開発を行い臨床試験に移行し、透析患者を減らせる社会的意義は大きい。
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Report
(4 results)
Research Products
(33 results)
