2021 Fiscal Year Final Research Report
Evaluation of the role of endothelial pannexin1 in progression of diabetic kidney disease
| Project/Area Number |
19K17757
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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 | Kawasaki Medical School |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 糖尿病性腎臓病 / ポドサイト障害 / ATP / Pannexin1 |
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| Outline of Final Research Achievements |
We hypothesized and investigated the hypothesis that vascular endothelium-derived ATP under hyperglycemia increases calcium influx into podocytes through purinergic(P2) receptor and promotes podocyte damage. In human glomerular endothelial cells, hyperglycemia and NOS inhibition increased ATP levels in the supernatant. Pannexin 1 inhibitor, probenecid, supressed the ATP release. Diabetic mice with endothelial dysfunction had elevated plasma ATP levels, albuminuria, and calcium levels in podocytes, which were suppressed by probenecid administration. The importance of the ATP / P2 receptor pathway was suggested in the development of podocyte injury in diabetic kidney disease.
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| Free Research Field |
糖尿病性腎臓病
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| Academic Significance and Societal Importance of the Research Achievements |
本邦での慢性腎臓病患者はは約1200万人と推計される、高齢化を反映し増加傾向にある。透析に至る疾患の第一位である糖尿病性腎臓病を初めとした多くの腎疾患には有効な治療法は少なく、その病態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。糖尿病性腎臓病をはじめとした様々な腎疾患において、podocyte障害は糸球体硬化への進展における初期病変であり、近年カルシウム動態異常の関与が強く示唆されている。ATP-Pannexin1-P2受容体経路のポドサイト障害の関与は新規のpodocyte障害経路であると考えられ、今後の治療標的となりうると考えられる。
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