2006 Fiscal Year Final Research Report Summary
Evidence base treatment of renal osteodistropy
| Project/Area Number |
17590066
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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 | Nihon Pharmaceutical University |
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Principal Investigator |
SHINKI Toshimasa Nihon Pharmaceutical University, Professor, 薬学部, 教授 (90138420)
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| Co-Investigator(Kenkyū-buntansha) |
SAKURADA Chikai Nihon Pharmaceutical University, Associate professor, 薬学部, 准教授 (30279244)
NAKAJIMA Takanori Nihon Pharmaceutical University, Associate professor, 薬学部, 准教授 (80265404)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Kidney / Renal osteodystrophy / Vitamin D / Parathyroid hormone / Transgenic / Bone mineral / Vitamin D metabolism / Proteomics |
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| Research Abstract |
24-Hydroxylase (CYP24) is an enzyme distributed in the target tissues of 1α,25-dihydroxyvitamin D_3 [1α,25(OH)_2D_3]. Two functions for this enzyme have been reported: One is production of 24,25-dihydroxyvitamin D_3 [24,25(OH)_2D_3] and the other is inactivation of 1α,25(OH)_2D_3. To elucidate other physiologic roles of CYP24 in vivo, we previously generated rats that constitutively express the CYP24 gene. These transgenic (Tg) rats developed unexpected phenotypes, such as low plasma levels of 24,25(OH)_2D_3, lipidemia, and albuminuria. In this study, we elucidated the mechanisms for inducing low plasma 24,25(OH)_2D_3 levels and bone loss. Tg rats excreted massive amounts of vitamin D binding protein (DBP), which coincided with the loss of albumin. In Tg rats, the renal expression pattern of megalin, which serves as an endocytotic receptor responsible for the reuptake of urinary proteins such as DBP and albumin, was identical to that of the wild-type rats. Excreted albumin appeared to compete for the binding and reabsorption of the DBP-25-hydroxyvitamin D_3 [25(OH)D_3] complex with megalin, resulting in a loss of 25(OH)D_3 into the urine and subsequent reduction of plasma 24,25(OH)_2D_3. In this prominent rat model of nephritis, supplementation of 25(OH)D_3 was effective in preventing bone loss in an early stage of renal insufficiency.
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[Book] NEW生化学2006
Author(s)
新木敏正 他
Total Pages
537
Publisher
廣川書店
Description
「研究成果報告書概要(和文)」より
