| Project/Area Number |
17K16105
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Kidney internal medicine
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| Research Institution | Kawasaki Medical School |
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Principal Investigator |
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| Research Collaborator |
Kashihara Naoki
Satoh Minoru
Nagasu Hajime
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 糖尿病性腎臓病 / 内皮-上皮連関 / 内皮細胞障害 / ATP / in vivo imaging / 糸球体内皮-上皮連関 / 内皮機能障害 / 糸球体上皮障害 / P2受容体 / 血漿中ATPレベル / 内皮アポトーシス / 糖尿病性腎障害 / 内皮上皮連関 / ATP感受性イオンチャネル型受容体 |
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| Outline of Final Research Achievements |
We have hypothesized that ATP release from endothelial cells with low NO bioavailability was increased, and endothelium-derived ATP induces Ca 2+ influx in glomerular epithelial cells and promotes epithelial dysfunction in the process of glomerular injury in diabetic kidney disease (DKD). In diabetic mice with endothelial dysfunction (eNOS-KO / STZ), plasma ATP levels and urinary albumin excretion were significantly increased compared to STZ mice. In eNOS-KO / STZ mice, Ca 2+ -sensitive fluorescent protein expression in podocyte was higher than in STZ. These results suggest that the progression of epithelial cell injury in DKD is related to increased intracellular Ca 2+ concentration and enhanced by endothelial injury.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病性腎臓病(DKD)は透析に至る疾患の第一位であり、その発症・進展機序の解明および治療法の確立は喫緊の課題と認識されている。これまでの腎臓病研究の多くが単一細胞に焦点を当てたものであるが、生理的機能の維持あるいは病態進展過程においても細胞間の相互作用の存在が強く示唆されている。本研究は内皮-上皮連関に着目し、障害内皮から放出されるATPが糸球体上皮細胞障害を増強させる可能性があることを見出し、新規治療開発に寄与しうる研究であると考える。
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