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Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling

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Abstract

Background

Hyperphosphatemia is common in chronic kidney disease and is associated with morbidity and mortality. The intestinal Na+-dependent phosphate transporter Npt2b is thought to be an important molecular target for the prevention of hyperphosphatemia. The role of Npt2b in the net absorption of inorganic phosphate (Pi), however, is controversial.

Methods

In the present study, we made tamoxifen-inducible Npt2b conditional knockout (CKO) mice to analyze systemic Pi metabolism, including intestinal Pi absorption.

Results

Although the Na+-dependent Pi transport in brush-border membrane vesicle uptake levels was significantly decreased in the distal intestine of Npt2b CKO mice compared with control mice, plasma Pi and fecal Pi excretion levels were not significantly different. Data obtained using the intestinal loop technique showed that Pi uptake in Npt2b CKO mice was not affected at a Pi concentration of 4 mM, which is considered the typical luminal Pi concentration after meals in mice. Claudin, which may be involved in paracellular pathways, as well as claudin-2, 12, and 15 protein levels were significantly decreased in the Npt2b CKO mice. Thus, Npt2b deficiency did not affect Pi absorption within the range of Pi concentrations that normally occurs after meals.

Conclusion

These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency.

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Acknowledgements

This work was supported by Grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan (26461254 to H.S. and 26293204 to K.M.), and The Salt Science Research Foundation (Japan). We thank Ms. Y. Oikawa, Ms. C. Honda, Mr. T. Tachibe, Ms. C. Goto, Mr. K. Matsumoto, Mr. K. Sato, Mr. M. Morita, and Ms. S. Uchida for skillful cooperation in establishment of NaPi2b CKO mouse line. Furthermore, we are grateful to Drs. Sachiko Tsukita and Tamura Atsushi (Osaka University) for scientific discussion.

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Authors and Affiliations

  1. Department of Molecular Nutrition, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto-Cho, Tokushima, Tokushima, 770-8503, Japan

    Kayo Ikuta, Hiroko Segawa, Shohei Sasaki, Ai Hanazaki, Toru Fujii, Aoi Kushi, Yuka Kawabata, Ruri Kirino, Sumire Sasaki, Miwa Noguchi, Ichiro Kaneko, Sawako Tatsumi & Ken-ichi Miyamoto

  2. Fuji Gotemba Research Labs., Research Division, Chugai Pharmaceutical Co., Ltd., 1-135, Komakado, Gotemba, Shizuoka, Japan

    Otoya Ueda, Naoko A. Wada, Shuichi Ohtomo, Yasuhiro Ichida, Akira Maeda, Kou-ichi Jishage & Naoshi Horiba

  3. Chugai Research Institute for Medical Science, Inc., 1-135, Komakado, Gotemba, Shizuoka, Japan

    Hiromi Tateishi, Mami Kakefuda, Yosuke Kawase & Kou-ichi Jishage

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  1. Kayo Ikuta
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Corresponding author

Correspondence to Hiroko Segawa.

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Conflict of interest

KI, HS, Shohei S, AH, TF, AK, YK, RK, SS, MN, IK, ST, and KM have declared that no conflict of interest exists. OU, NW, SO, YI, AM, KJ, and NH are employees of Chugai Pharmaceutical Co., Ltd. HT, MK, YK, and KJ are Chugai Research Institute for Medical Science, Inc.

Human and animal rights

Mice were handled in accordance with the Guidelines for Animal Experimentation of Tokushima University School of Medicine and with the Guidelines for the Care and Use of Laboratory Animals at Chugai Pharmaceuticals. This article does not contain any studies with human participants.

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Ikuta, K., Segawa, H., Sasaki, S. et al. Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling. Clin Exp Nephrol 22, 517–528 (2018). https://doi.org/10.1007/s10157-017-1497-3

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