Effect of variations in dietary Pi intake on intestinal Pi transporters (NaPi-IIb, PiT-1, and PiT-2) and phosphate-regulating factors (PTH, FGF-23, and MEPE)
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Hyperphosphatemia is a common condition in patients with chronic kidney disease (CKD) and can lead to bone disease, vascular calcification, and increased risks of cardiovascular disease and mortality. Inorganic phosphate (Pi) is absorbed in the intestine, an important step in the maintenance of homeostasis. In CKD, it is not clear to what extent Pi absorption is modulated by dietary Pi. Thus, we investigated 5/6 nephrectomized (Nx) Wistar rats to test whether acute variations in dietary Pi concentration over 2 days would alter hormones involved in Pi metabolism, expression of sodium-phosphate cotransporters, apoptosis, and the expression of matrix extracellular phosphoglycoprotein (MEPE) in different segments of the small intestine. The animals were divided into groups receiving different levels of dietary phosphate: low (Nx/LPi), normal (Nx/NPi), and high (Nx/HPi). Serum phosphate, fractional excretion of phosphate, intact serum fibroblast growth factor 23 (FGF-23), and parathyroid hormone (PTH) were significantly higher and ionized calcium was significantly lower in the Nx/HPi group than in the Nx/LPi group. The expression levels of NaPi-IIb and PiT-1/2 were increased in the total jejunum mucosa of the Nx/LPi group compared with the Nx/HPi group. Modification of Pi concentration in the diet affected the apoptosis of enterocytes, particularly with Pi overload. MEPE expression was higher in the Nx/HPi group than in the Nx/NPi. These data reveal the importance of early control of Pi in uremia to prevent an increase in serum PTH and FGF-23. Uremia may be a determining factor that explains the expressional modulation of the cotransporters in the small intestine segments.
KeywordsIntestinal absorption Sodium-phosphate cotransporters Apoptosis MEPE Uremia
Messenger ribonucleic acid
Fractional excretion of phosphate
Fibroblast growth factor 23
Polymerase chain reaction
Reverse transcriptase-quantitative PCR
The authors thank Flávia Gomes Machado and Walter Campestre for the care and management of the animals. We also thank Prof. Dr. Patrícia Gama from the University of São Paulo for the earlier support of this project.
TMA and VJ conceived and designed the research; TMA, FRS, and EMCO performed the experiments; TMA, FRS, WVD, and PC analyzed the data; TMA, FRS, LMR, WVD, and VJ interpreted the results of the experiments; TMA, FRS, and WVD prepared the figures; TMA and FRS drafted the manuscript; TMA, FRS, LMR, RMAM, and VJ edited and revised the manuscript. All authors read and approved the final version of the manuscript.
Compliance with ethical standards
This study was supported by grants from the Fundação de Amparo à Pesquisa do Estado de São Paulo (São Paulo State Research Foundation—grant number 2011/00036-0).
Conflict of interest
The authors declare that they have no conflicts of interest.
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