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01.06.2018 | Original article

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

verfasst von: Kayo Ikuta, Hiroko Segawa, Shohei Sasaki, Ai Hanazaki, Toru Fujii, Aoi Kushi, Yuka Kawabata, Ruri Kirino, Sumire Sasaki, Miwa Noguchi, Ichiro Kaneko, Sawako Tatsumi, Otoya Ueda, Naoko A. Wada, Hiromi Tateishi, Mami Kakefuda, Yosuke Kawase, Shuichi Ohtomo, Yasuhiro Ichida, Akira Maeda, Kou-ichi Jishage, Naoshi Horiba, Ken-ichi Miyamoto

Erschienen in: Clinical and Experimental Nephrology | Ausgabe 3/2018

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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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Titel: Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling
verfasst von: Kayo Ikuta
Hiroko Segawa
Shohei Sasaki
Ai Hanazaki
Toru Fujii
Aoi Kushi
Yuka Kawabata
Ruri Kirino
Sumire Sasaki
Miwa Noguchi
Ichiro Kaneko
Sawako Tatsumi
Otoya Ueda
Naoko A. Wada
Hiromi Tateishi
Mami Kakefuda
Yosuke Kawase
Shuichi Ohtomo
Yasuhiro Ichida
Akira Maeda
Kou-ichi Jishage
Naoshi Horiba
Ken-ichi Miyamoto
Publikationsdatum: 01.06.2018
Verlag: Springer Singapore
Erschienen in: Clinical and Experimental Nephrology / Ausgabe 3/2018
Print ISSN: 1342-1751
Elektronische ISSN: 1437-7799
DOI: https://doi.org/10.1007/s10157-017-1497-3

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