Systemic network for dietary inorganic phosphate adaptation among three organs

Ikuta, Kayo; Segawa, Hiroko; Hanazaki, Ai; Fujii, Tomoyuki; Kaneko, Ichiro; Shiozaki, Yuji; Tatsumi, Sawako; Ishikawa, Yasuko; Miyamoto, Ken‐ichi

doi:10.1007/s00424-018-2242-9

Cited by 11 publications

(25 citation statements)

References 30 publications

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“…The mice were individually placed in metabolic cages at 10:00 a.m. for quantitative urine and fecal collection for 24 hr with free access to food and water. Fecal samples were ashed according to a modified protocol (Ikuta et al, ; Ikuta et al, ). The fecal samples were collected and placed in beakers and allowed to dry at 110°C for no more than 24 hr.…”

Section: Methodsmentioning

confidence: 99%

Role of sodium‐dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages

et al. 2020

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SLC34A3/NPT2c/NaPi‐2c/Npt2c is a growth‐related NaPi cotransporter that mediates the uptake of renal sodium‐dependent phosphate (Pi). Mutation of human NPT2c causes hereditary hypophosphatemic rickets with hypercalciuria. Mice with Npt2c knockout, however, exhibit normal Pi metabolism. To investigate the role of Npt2c in Pi homeostasis, we generated α‐klotho−/−/Npt2c−/− (KL2cDKO) mice and analyzed Pi homeostasis. α‐Klotho−/− (KLKO) mice exhibit hyperphosphatemia and markedly increased kidney Npt2c protein levels. Genetic disruption of Npt2c extended the lifespan of KLKO mice similar to that of α‐Klotho−/−/Npt2a−/− mice. Adult KL2cDKO mice had hyperphosphatemia, but analysis of Pi metabolism revealed significantly decreased intestinal and renal Pi (re)absorption compared with KLKO mice. The 1,25‐dihydroxy vitamin D3 concentration was not reduced in KL2cDKO mice compared with that in KLKO mice. The KL2cDKO mice had less severe soft tissue and vascular calcification compared with KLKO mice. Juvenile KL2cDKO mice had significantly reduced plasma Pi levels, but Pi metabolism was not changed. In Npt2cKO mice, plasma Pi levels began to decrease around the age of 15 days and significant hypophosphatemia developed within 21 days. The findings of the present study suggest that Npt2c contributes to regulating plasma Pi levels in the juvenile stage and affects Pi retention in the soft and vascular tissues in KLKO mice.

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Section: Methodsmentioning

confidence: 99%

Role of sodium‐dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages

et al. 2020

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“…For the dietary adaptation study, mice were fed a test diet based on modified AIN93G (low Pi; 0.02 or 0.1% Pi, control Pi; 0.6% Pi, and high Pi; 1.2% Pi), as described previously [47][48][49] .…”

Section: Dietary Adaptationmentioning

confidence: 99%

“…The PCR reaction was examined without reverse transcriptase (data not shown). Quantitative PCR was performed using ABI PRISM 7500 (Applied Biosystems, Foster City, CA) as described previously 34,47,49,52,53 . The reaction mixture consisted of 10 µl of SYBR Premix Ex Taq, ROX Reference Dye II (Perfect Real Time, Takara, Osaka, Japan) with specific primers (Table 2).…”

Section: Rna Extraction Cdna Synthesis and Quantitative Pcrmentioning

confidence: 99%

“…BBMVs prepared using the Ca 2+ precipitation method, cortical membrane, and whole homogenate were obtained from mouse kidneys and used for immunoblotting and immunoprecipitation analyses as described previously 34,49,52,53 . Protein samples were heated at 95°C for 5 min in sample buffer in the presence of 2-mercaptoethanol and subjected to sodium dodecyl sulfatepolyacrylamide gel electrophoresis (SDS-PAGE).…”

Section: Protein Sample Purification and Immunoblottingmentioning

confidence: 99%

“…The separated proteins were transferred by electrophoresis to Immobilon-P polyvinylidene difluoride (Millipore, Billerica, MA, USA) and treated with diluted antibodies. Signals were detected using Immobilon Western (Millipore) 34,49,52,53 .…”

Section: Protein Sample Purification and Immunoblottingmentioning

confidence: 99%

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Phosphate Transporter Regulator That Prevents Abnormal Hyperphosphatemia.

Sasaki

Shiozaki

Hanazaki

et al. 2021

Preprint

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Renal type II sodium-dependent inorganic phosphate (Pi) transporters NaPi2a and NaPi2c cooperate with other organs to strictly regulate the plasma Pi concentration. A high Pi load induces the phosphaturic hormones parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), enhances urinary Pi excretion and prevents the onset of hyperphosphatemia. How FGF23 is induced from the bones by a high Pi load and the setpoint of the plasma Pi concentration, however, are unclear. Here, we investigated the role of transporter-associated protein (TRAP), found in gene co-expression networks in NaPi2a and NaPi2c function. TRAP is localized in the renal proximal tubules and interacts with NaPi2a. In TRAP-knockout (KO) mice, the serum FGF23 concentration was markedly increased but increased Pi excretion and hypophosphatemia were not observed. In addition, TRAP-KO mice exhibit reduced NaPi2a responsiveness to FGF23 and PTH administration. Furthermore, a dietary Pi load causes marked hyperphosphatemia and abnormal NaPi2a regulation in TRAP-KO mice. Thus, TRAP is thought to be associated with FGF23 induction in bones and the regulation of NaPi2a to prevent an increase in the plasma Pi concentration due to a high Pi load and kidney injury.

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Expression of phosphate and calcium transporters and their regulators in parotid glands of mice

Moser

Haykir

Küng

et al. 2022

Pflugers Arch - Eur J Physiol

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The concentration of inorganic phosphate (Pi) in plasma is under hormonal control, with deviations from normal values promptly corrected to avoid hyper- or hypophosphatemia. Major regulators include parathyroid hormone (PTH), fibroblast growth factor 23 (FGF-23), and active vitamin D3 (calcitriol). This control is achieved by mechanisms largely dependent on regulating intestinal absorption and renal excretion, whose combined actions stabilise plasma Pi levels at around 1–2 mM. Instead, Pi concentrations up to 13 and 40 mM have been measured in saliva from humans and ruminants, respectively, suggesting that salivary glands have the capacity to concentrate Pi. Here we analysed the transcriptome of parotid glands, ileum, and kidneys of mice, to investigate their potential differences regarding the expression of genes responsible for epithelial transport of Pi as well as their known regulators. Given that Pi and Ca2+ homeostasis are tightly connected, the expression of genes involved in Ca2+ homeostasis was also included. In addition, we studied the effect of vitamin D3 treatment on the expression of Pi and Ca2+ regulating genes in the three major salivary glands. We found that parotid glands are equipped preferentially with Slc20 rather than with Slc34 Na+/Pi cotransporters, are suited to transport Ca2+ through the transcellular and paracellular route and are potential targets for PTH and vitamin D3 regulation.

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Systemic network for dietary inorganic phosphate adaptation among three organs

Cited by 11 publications

References 30 publications

Role of sodium‐dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages

Role of sodium‐dependent Pi transporter/Npt2c on Pi homeostasis in klotho knockout mice different properties between juvenile and adult stages

Phosphate Transporter Regulator That Prevents Abnormal Hyperphosphatemia.

Expression of phosphate and calcium transporters and their regulators in parotid glands of mice

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