Functional Relationship between the Molecules Involved in the Renal Phosphate Reabsorption
| Project/Area Number |
18590921
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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 |
Kidney internal medicine
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| Research Institution | Research Institute, Osaka Medical Center for Maternal and Child Health |
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Principal Investigator |
MICHIGAMI Toshimi Research Institute, Osaka Medical Center for Maternal and Child Health, Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Organization, Department of Bone and Mineral Research, Director (00301804)
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| Co-Investigator(Kenkyū-buntansha) |
KONDOU Hiroki Osaka Medical Center and Research Institute for Maternal and Child Health, Osaka Prefectural Organization, Researcher (10373515)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,830,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Keywords | phosphate / FGF23 / megain / klotho / Na^+ / Pi co-transporter / klotho / 無機リン酸 / ERK1 / 2 / ナトリウム・リン酸共輸送担体 / リン酸再吸収 / FGF-23 / megalin |
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| Research Abstract |
Although it has been revealed that several molecules are involved in the regulation of renal phosphate reabsorption, the functional relationship between these molecules remains to be elucidated. In the current study, we aimed to clarify the mechanisms by which these molecules coordinate to regulate renal phosphate reabsorption. We have previously found that megalin-dependent endocytosis is involved in renal phosphate reabsorption via the regulation of subcellular distribution of type IIa Na^+/Pi co-transporter. Therefore, we first examined whether megalin-dependent endocytosis affect the action of FGF23 as a phosphatunc hormone. The disturbance of megalin-dependent endocytosis using soluble form of receptor associated protein(RAP) resulted in the reduced serum level of FGF23 in mice. This observation recapitulates the reduced serum FGF23 in human patients with Fanconi syndrome, suggesting that FGF23 is filtered in glomerulus and excreted in urine. We also examined the effect of extracellular phosphate(Pi) itself on the FGF23 signaling using HEK293 human embryonic kidney cells. We found that increased extracellular Pi resulted in the signal transduction in the cells, and it shared the downstream signaling network with FGF23. These results suggest that extracellular Pi itself affect the responsiveness of renal tubular cells to FGF23.
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Report
(3 results)
Research Products
(23 results)
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[Journal Article] Clinical usefulness2008
Author(s)
Endo I, Fukumoto S, Ozono K, Namba N, Tanaka H, Inoue D, Minagawa M, Sugunoto T, Yamauchi M, Michigami T, Matsumoto T.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] The Sp1 family of transcription factors regulates the human alpha 2 (XI) collagen gene (COL11A2) in Saos-2 osteoblastic cells.2006
Author(s)
Goto T, Matsui Y, Fernandes RJ, Hanson DA, Kubo T, Yutaka K, Michigami T, Komori T, Fujita T, Yang L, Eyre DR, Yasui N.
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Journal Title
Journal of Bone and Miner Research 21・5
Pages: 661-673
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