| Project/Area Number |
18K08223
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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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| Review Section |
Basic Section 53040:Nephrology-related
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| Research Institution | Tokyo Medical University (2022)
Tokyo Women's Medical University (2018-2021) |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | カベオラ / カベオリン-1 / 糸球体上皮細胞 / 糸球体内皮細胞 / エンドサイトーシス / トランスサイトーシス / エキソサイトーシス / 細胞内通過経路 / アルブミン / 蛋白尿 / セルトラリン / ダイナミン阻害 |
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| Outline of Final Research Achievements |
We have reported the caveolae medicated intracellular trafficking pathway of albumin in glomerular endothelial cells.
In this study, we proofed albumin endocytosis through caveolae, transcytosis related with actin, endosome, and lysosomes, and then exocytosis, in glomerular epithelial cells as the intracellular traffickng pathway of albumin. Moreover, we observed the intracellular trafficking pathway of albumin by the electron microscope.
Since dynamin was related with caveolae internalization into cytoplasm, we used selective serotonin reuptake inhibitors, sertraline which had inhibitory effect of dynamin, and proofed its inhibitory effect of albumin internalization through caveolae into glomerular epithelial and endothelial cells, and the effect to reduce albuminuria in puromysin induced nephrotic syndrome modeled mice.
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| Academic Significance and Societal Importance of the Research Achievements |
これまでアルブミン尿の機序として内皮細胞におけるfenestraeや上皮細胞の足突起間のgapなど細胞間経路が考えられ、糸球体上皮・内皮細胞の細胞内通過経路に関する研究はほとんどされていなかったが、本研究により新機序として細胞内通過経路が証明され、更に薬剤によるネフローゼ症候群モデルマウスのアルブミン減少効果を証明できたことから、新たな慢性腎臓病の治療薬への発展につながる可能性を示すことができた。
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