Critical ops hack 0.9.11.f1474/1/2023 ![]() It may also be involved in the sensing of dietary phosphate composition and the release of hormonal factors that modulate renal phosphate reabsorption to achieve phosphate balance. ![]() Interestingly, studies using NaPi-IIb knockout mice with adenine-induced CKD show only partial attenuation of hyperphosphatemia, suggesting that an additional sodium-independent pathway is involved in phosphate absorption. The aim of this review is to discuss our current knowledge of the processes and role of the intestine in phosphate homeostasis and to provide evidence that this organ could be targeted for the treatment of hypophosphatemia and hyperphosphatemia. Inorganic phosphate (Pi) is an essential nutrient for the maintenance of cells. In healthy mammals, extracellular Pi is maintained within a narrow concentration range of 0.70 to 1.55 mM. Mammalian cells depend on Na+/Pi cotransporters for Pi absorption, which have been well studied. However, a new type of sodium-independent Pi transporter has been identified. ![]() This transporter assists in the absorption of Pi by intestinal cells and renal proximal tubule cells and in the reabsorption of Pi by osteoclasts and capillaries of the blood–brain barrier (BBB). Hyperphosphatemia is a risk factor for mineral deposition, the development of diseases such as osteoarthritis, and vascular calcifications (VCs). Na+-independent Pi transporters have been identified and biochemically characterized in vascular smooth muscle cells (VSMCs), chondrocytes, and matrix vesicles, and their involvement in mineral deposition in the extracellular microenvironment has been suggested. According to the growth rate hypothesis, cancer cells require more phosphate than healthy cells due to their rapid growth rates. Recently, it was demonstrated that breast cancer cells (MDA-MB-231) respond to high Pi concentration (2 mM) by decreasing Na+-dependent Pi transport activity concomitant with an increase in Na+-independent (H+-dependent) Pi transport. This Pi H+-dependent transport has a fundamental role in the proliferation and migratory capacity of MDA-MB-231 cells. The purpose of this review is to discuss experimental findings regarding Na+-independent inorganic phosphate transporters and summarize their roles in Pi homeostasis, cancers and other diseases, such as osteoarthritis, and in processes such as VC. Phosphorus (usually as phosphate) is an essential nutrient used for enzyme activation and the synthesis of adenosine triphosphate and other biomolecules. Most phosphorus in the body is sequestered in mineralized bone tissue and teeth. Phosphate homeostasis is maintained by FGF23 derived from bones and the kidney-derived cofactor Klotho. FGF23 binds the membrane-bound Klotho–FGF receptor complex with much higher affinity than the FGF receptor (FGFR) alone to generate downstream signaling events. Aberrations in FGF23, FGFR, or Klotho structure or expression result in dysregulation of serum phosphate levels in experimental animal models and human diseases. ![]() ![]() The FGF23–Klotho system suppresses sodium-phosphate cotransporters (NaPi2 family proteins) in proximal tubular epithelial cells in the kidney to induce urinary phosphate wasting. In addition, the FGF23–Klotho system also regulates vitamin D metabolism, which is an important factor that regulates the homeostasis of minerals such as calcium, phosphorus, and magnesium. ![]()
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