| Project/Area Number |
13672287
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
TAKANO Mikihisa Hiroshima University, Graduate School of Biomedical Sciences, Professor, 大学院・医歯薬学総合研究科, 教授 (20211336)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAI Junya Hiroshima University, Graduate School of Biomedical Sciences, Research Associate, 大学院・医歯薬学総合研究科, 助手 (20301301)
MURAKAMI Teruo Hiroshima University, Graduate School of Biomedical Sciences, Associate Professor, 大学院・医歯薬学総合研究科, 助教授 (20136055)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | Dent's disease / chloride channel / ClC-5 / endocytosis / proteinuria / hypercalciuria / receptor / renal tubules / 高カルシウム尿症 / 培養腎上皮細胞 / エンドソーム内酸性化 / 蛋白尿 / 遺伝性腎疾患 |
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| Research Abstract |
Dent's disease is a X-linked recessive nephrolithiasis associated with various renal dysfunctions such as proteinuria and hypercalciuria. Recently, CLCN5, a gene encoding chloride channel ClC-5, was found to be responsible for Dent's disease, though the precise role of ClC-5 is not known at this moment. ClC-5 is highly expressed in the kidney, where the channel is involved in the acidification of endosomes, an important step for receptor-mediated endocytosis. On the other hand, proteins filtered through glomerulus are efficiently taken up by tubular cells by receptor-mediated endocytosis. In the present study, I examined the role of ClC-5 in renal handling of proteins and calcium.
Cultured renal epithelial cells OK were used as a model system, which I confirmed the expression of ClC-5. When cells were treated with chloride channel inhibitors, the endocytosis of FITC-labeled albumin was inhibited. In addition, the uptake of calcium by OK cells was inhibited by chloride channel inhibitors as well as by anti-ClC-5 antibody. Therefore, C1C-5 would have an important role for the endocytosis of filtered protein and calcium uptake in the kidney. These results may explain the proteinuria and hypercalciuria observed in Dent's disease, in which ClC-5 is lacking.
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