Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b<sup>+/−</sup>mice
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- Akiko Ohi
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Etsuyo Hanabusa
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Otoya Ueda
- Chugai Pharmaceutical Company, Limited, and
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- Hiroko Segawa
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Naoshi Horiba
- Chugai Pharmaceutical Company, Limited, and
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- Ichiro Kaneko
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Shoji Kuwahara
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Tomo Mukai
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Shohei Sasaki
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Rieko Tominaga
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Junya Furutani
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Fumito Aranami
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Shuichi Ohtomo
- Chugai Pharmaceutical Company, Limited, and
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- Yumiko Oikawa
- Chugai Research Institute for Medical Science, Incorporated, Tokyo, Japan
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- Yousuke Kawase
- Chugai Research Institute for Medical Science, Incorporated, Tokyo, Japan
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- Naoko A. Wada
- Chugai Research Institute for Medical Science, Incorporated, Tokyo, Japan
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- Takanori Tachibe
- Chugai Research Institute for Medical Science, Incorporated, Tokyo, Japan
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- Mami Kakefuda
- Chugai Research Institute for Medical Science, Incorporated, Tokyo, Japan
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- Hiromi Tateishi
- Chugai Research Institute for Medical Science, Incorporated, Tokyo, Japan
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- Kaoru Matsumoto
- Chugai Research Institute for Medical Science, Incorporated, Tokyo, Japan
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- Sawako Tatsumi
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Shinsuke Kido
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
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- Naoshi Fukushima
- Chugai Pharmaceutical Company, Limited, and
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- Kou-ichi Jishage
- Chugai Pharmaceutical Company, Limited, and
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- Ken-ichi Miyamoto
- Department of Molecular Nutrition Institute of Health Biosciences, University of Tokushima Graduate School, Tokushima City; and
書誌事項
- 公開日
- 2011-11
- 資源種別
- journal article
- DOI
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- 10.1152/ajprenal.00663.2010
- 公開者
- American Physiological Society
この論文をさがす
説明
<jats:p>An inorganic phosphate (P<jats:sub>i</jats:sub>)-restricted diet is important for patients with chronic kidney disease and patients on hemodialysis. Phosphate binders are essential for preventing hyperphosphatemia and ectopic calcification. The sodium-dependent P<jats:sub>i</jats:sub>(Na/P<jats:sub>i</jats:sub>) transport system is involved in intestinal P<jats:sub>i</jats:sub>absorption and is regulated by several factors. The type II sodium-dependent P<jats:sub>i</jats:sub>transporter Npt2b is expressed in the brush-border membrane in intestinal epithelial cells and transports P<jats:sub>i</jats:sub>. In the present study, we analyzed the phenotype of Npt2b<jats:sup>−/−</jats:sup>and hetero<jats:sup>+/−</jats:sup>mice. Npt2b<jats:sup>−/−</jats:sup>mice died in utero soon after implantation, indicating that Npt2b is essential for early embryonic development. At 4 wk of age, Npt2b<jats:sup>+/−</jats:sup>mice showed hypophosphatemia and low urinary P<jats:sub>i</jats:sub>excretion. Plasma fibroblast growth factor 23 levels were significantly decreased and 1,25(OH)<jats:sub>2</jats:sub>D<jats:sub>3</jats:sub>levels were significantly increased in Npt2b<jats:sup>+/−</jats:sup>mice compared with Npt2b<jats:sup>+/+</jats:sup>mice. Npt2b mRNA levels were reduced to 50% that in Npt2b<jats:sup>+/+</jats:sup>mice. In contrast, renal Npt2a and Npt2c transporter protein levels were significantly increased in Npt2b<jats:sup>+/−</jats:sup>mice. At 20 wk of age, Npt2b<jats:sup>+/−</jats:sup>mice showed hypophosphaturia and reduced Na/P<jats:sub>i</jats:sub>cotransport activity in the distal intestine. Npt2b<jats:sup>+/+</jats:sup>mice with adenine-induced renal failure had hyperphosphatemia and high plasma creatinine levels. Npt2b<jats:sup>+/−</jats:sup>mice treated with adenine had significantly reduced plasma P<jats:sub>i</jats:sub>levels compared with Npt2b<jats:sup>+/+</jats:sup>mice. Intestinal Npt2b protein and Na<jats:sup>+</jats:sup>/P<jats:sub>i</jats:sub>transport activity levels were significantly lower in Npt2b<jats:sup>+/−</jats:sup>mice than in the Npt2b<jats:sup>+/+</jats:sup>mice. The findings of the present studies suggest that Npt2b is an important target for the prevention of hyperphosphatemia.</jats:p>
収録刊行物
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- American Journal of Physiology-Renal Physiology
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American Journal of Physiology-Renal Physiology 301 (5), F1105-F1113, 2011-11
American Physiological Society