Effect of Npt2b deletion on intestinal and renal inorganic phosphate (Pi) handling
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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.
In the present study, we made tamoxifen-inducible Npt2b conditional knockout (CKO) mice to analyze systemic Pi metabolism, including intestinal Pi absorption.
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.
These findings indicate that abnormal Pi metabolism may also be involved in tight junction molecules such as Cldns that are affected by Npt2b deficiency.
KeywordsIntestine Transcellular transport–paracellular transport
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.
Compliance with ethical standards
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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