2015 Fiscal Year Final Research Report
Molecular mechanism of transportsome in chronic kidney disease and the involvement of thyroid hormone
| Project/Area Number |
25460652
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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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| Research Field |
Applied pharmacology
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
MARUYAMA Toru 熊本大学, 薬学部, 教授 (90423657)
OTAGIRI Masaki 崇城大学, 薬学部, 教授 (80120145)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Keywords | 腎障害 / 二次性副甲状腺機能亢進症 / 副甲状腺ホルモン |
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| Outline of Final Research Achievements |
Hyperuricemia occurs with increasing frequency among patients with hyperparathyroidism. However, the molecular mechanism by which serum parathyroid hormone (PTH) regulates serum urate levels remains unknown. Here we show that, in rats with secondary hyperparathyroidism (SHPT), serum urate levels are increased and urate excretion in the intestine and kidney is decreased, presumably due to the downreguration of the intestinal and renal membrane expression of a urate exporter ABCG2. These effects were prevented by the administration of the calcimimetic PTH suppressor, cinacalcet. In Caco-2 cells, the plasma membrane expression of ABCG2 was downregulated by PTH. Clinical studies showed that treatment with cinacalcet resulted in significant reductions in serum urate levels in SHPT patients. These results suggest that PTH downregulates ABCG2 expression, and thereby suppresses intestinal and renal urate excretion, and that the effects of PTH can be prevented by a cinacalcet treatment.
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| Free Research Field |
医療薬学
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