| Project/Area Number |
16K19479
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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 | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
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| Keywords | ポドサイト / 蛋白尿 / ネフローゼ症候群 / スリット膜 / Ephrin-B1 / Nephrin / JNK / NHERF2 / Par-6 / リン酸化 / Ephrin-B2 / ノックアウトマウス / 糸球体 / 腎臓学 |
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| Outline of Final Research Achievements |
We previously reported that ephrin-B1 is localized at the slit diaphragm of glomerular podocytes. However, the function of ephrin-B1 at this location is unclear. We show that podocyte-specific ephrin-B1 conditional knockout mice displayed alteration of the podocyte morphology, disarrangement of the slit diaphragm molecules, and proteinuria. Analyses with the HEK cell expression system revealed that ephrin-B1 interacted with nephrin via the basal regions of extracellular domain. Nephrin-binding ephrin-B1 was phosphorylated by extracellular nephrin stimulation. The phosphorylation of ephrin-B1 was detected in rat glomeruli of the nephrotic model, induced by anti-nephrin antibody injection. Ephrin-B1 regulated the phosphorylation of JNK in glomeruli. Taken together, it is conceivable that ephrin-B1 in the podocyte is essential for maintaining the integrity of the glomerular filtration barrier and plays a critical role as a signal molecule controlling the podocyte functions.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究で、スリット膜のバリア機能維持におけるEphrin-B1の役割を解明し、蛋白尿発症の新たな分子機構を明らかにした。また、ネフローゼ症候群の症例でEphrin-B1の発現が低下していることを発見した。Ephrin-B1の発現低下の抑制、リン酸化抑制、JNK活性を制御する薬剤、化合物が蛋白尿治療薬として有効である可能性を示した。
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