2003 Fiscal Year Final Research Report Summary
Fibroblast growth factor 23 in renal phosphate reabsorption and vitamin D metabolism
| Project/Area Number |
14370320
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | The University of Tokushima |
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Principal Investigator |
MIYAMOTO Kenichi The University of Tokushima, School of Medicine, Professor, 医学部, 教授 (70174208)
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| Co-Investigator(Kenkyū-buntansha) |
SEGAWA Hiroko The University of Tokushima, School of Medicine, Assistant professor, 医学部, 助手 (70325257)
ITHO Mikiko The University of Tokushima, School of Medicine, Assistant professor, 医学部, 助手 (50314852)
KUWAHATA Masashi The University of Tokushima, School of Medicine, Associate professor, 医学部, 講師 (30304512)
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| Project Period (FY) |
2002 – 2003
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| Keywords | FGF23 / phosphate / kidney / phosphatonin / receptor |
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| Research Abstract |
Fibroblast growth factor 23 (FGF23), a phosphaturic factor, is involved in the regulation of renal Pi reabsocption. Proteolysis-resistant FGF23 mutants expressed in rodents reduce Pi uptake in both intestine and kidney, independent of parathyroid hormone action. In the present study, we investigated whether FGF23 affect dietary regulation of Na^+-dependent Pi (Na/Pi) cotransport in rat kidney using wild-type FGF23 and an R 179Q mutant, which disrupts a consensus proteolytic cleavage motif
Rats injected with naked human FGF23 DNA (wild type or R 179Q mutant) expressed human FGF23 transcript in the liver. In those animals, the plasma calcium and parathyroid hormone levels were not affected by FGF23 (either wild type or R179Q mutant). FGF23-R179Q did, however, significantly decrease the plasma Pi and renal Na/Pi cotransport activity and also the levels of type IIc Na/Pi cotransporter proteins in BBMVs from normal rat kidney. In rats fed a low Pi diet, the levels of type IIa and type IIc Na/Pi cotransporters were markedly ink in Western blotting and immunohistochemical analyses. After injection of FGF23-R 179Q DNA into the rats fed a low Pi diet, the levels of the type IIa and type IIc transporter proteins were decreased. Thus FGF23 mutant blunts the signaling of Pi deprivation in renal type II Na/Pi cotransporters, suggesting that the FGF23 pathway could be involved in the signaling of dietary Pi
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