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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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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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 / トランスポーター / 尿毒症物質 / 甲状腺ホルモン / 腎疾患 / 慢性腎障害 |
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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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Report
(4 results)
Research Products
(20 results)
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[Journal Article] p-Cresyl sulfate, a uremic toxin, causes vascular endothelial and smooth muscle cell damages by inducing oxidative stress.2015
Author(s)
Watanabe H, Miyamoto Y, Enoki Y, Ishima Y, Kadowaki D, Kotani S, Nakajima M, Tanaka M, Matsushita K, Mori Y, Kakuta T, Fukagawa M, Otagiri M, Maruyama T
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Journal Title
Pharmacol Res Perspect
Volume: 3
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Human organic anion transporters function as a high-capacity transporter for p-cresyl sulfate, a uremic toxin2014
Author(s)
Watanabe H, Sakaguchi Y, Sugimoto R, Kaneko K, Iwata H, Kotani S, Nakajima M, Ishima Y, Otagiri M, Maruyama T
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Journal Title
Clin Exp Nephrol
Volume: 18
Issue: 5
Pages: 814-20
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] S-nitrosated α-1-acid glycoprotein kills drug-resistant bacteria and aids survival in sepsis2013
Author(s)
Watanabe K, Ishima Y, Akaike T, Sawa T, Kuroda T, Ogawa W, Watanabe H, Suenaga A, Kai T, Otagiri M, Maruyama T
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Journal Title
FASEB J
Volume: 27
Pages: 391-398
Related Report
Peer Reviewed
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