CASEIN KINASE2-Dependent Phosphorylation of PHOSPHATE2 Fine-tunes Phosphate Homeostasis in Rice

AbstractObjectivesPhosphate is essential for skeletal mineralization, which is regulated by parathyroid hormone, calcitriol and fibroblast growth factor 23 (FGF23). Serum phosphate is physiologically higher in younger children, but factors that contribute to this physiological state are poorly understood. This study aimed to evaluate phosphate and its regulators in children compared with adults.Materials and methodsThe participants were children aged 3–11 years and adults older than 20 years of age. Biochemical parameters including calcium, phosphorus, alkaline phosphatase, FGF23, and vitamin D were measured. Fractional excretion of phosphate was calculated, using serum and urine phosphate and creatinine.ResultsThis cross-sectional study was conducted on 45 children (mean age: 9.0 ± 2.1) and 44 adults (mean age: 38.9 ± 11.1). The children had higher serum calcium, phosphate, alkaline phosphatase, and FGF23 (p < 0.001), but fractional excretion of phosphate was greater in adults (14.1 ± 5.7, 11.4 ± 4.4, p = 0.019, 95% confidence interval [CI]: −0.7 to −0.2). Of all individuals, 61.8% had vitamin D deficiency. By multiple regression analysis, entering age, calcium, phosphate, and vitamin D level, the only independent predictor of FGF23 was 1, 25 dihydroxy-vitamin D3 (β: 0.78, p < 0.001, 95% CI: 0.5–1.1, R2: 0.59 for children, and β: 0.59, p < 0.001, 95% CI: 0.5–1.4, R2: 0.45 for adults).ConclusionAs far as we know, there is little information regarding the role of FGF23 in physiologic state. In this cross-sectional study no association was found between FGF23 and urinary phosphate excretion in growing children. Further studies with more detail are essential to evaluate phosphate homeostasis during childhood.

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Stamp2 Controls Macrophage Inflammation through Nicotinamide Adenine Dinucleotide Phosphate Homeostasis and Protects against Atherosclerosis

Cell Metabolism ◽

10.1016/j.cmet.2012.05.009 ◽

2012 ◽

Vol 16 (1) ◽

pp. 81-89 ◽

Cited By ~ 21

Author(s):

Henrik ten Freyhaus ◽

Ediz S. Calay ◽

Abdullah Yalcin ◽

Sara N. Vallerie ◽

Ling Yang ◽

...

Keyword(s):

Nicotinamide Adenine Dinucleotide ◽

Nicotinamide Adenine Dinucleotide Phosphate ◽

Nicotinamide Adenine ◽

Phosphate Homeostasis

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The Complexities of Organ Crosstalk in Phosphate Homeostasis: Time to Put Phosphate Sensing Back in the Limelight

International Journal of Molecular Sciences ◽

10.3390/ijms22115701 ◽

2021 ◽

Vol 22 (11) ◽

pp. 5701

Author(s):

Lucile Figueres ◽

Sarah Beck-Cormier ◽

Laurent Beck ◽

Joanne Marks

Keyword(s):

Molecular Mechanisms ◽

Dominant Role ◽

Fibroblast Growth Factor 23 ◽

Hormone Secretion ◽

Phosphate Transport ◽

Phosphate Homeostasis ◽

Cellular Mechanisms ◽

Exact Function ◽

Phosphate Sensing ◽

Significant Research

Phosphate homeostasis is essential for health and is achieved via interaction between the bone, kidney, small intestine, and parathyroid glands and via intricate processes involving phosphate transporters, phosphate sensors, and circulating hormones. Numerous genetic and acquired disorders are associated with disruption in these processes and can lead to significant morbidity and mortality. The role of the kidney in phosphate homeostasis is well known, although it is recognized that the cellular mechanisms in murine models and humans are different. Intestinal phosphate transport also appears to differ in humans and rodents, with recent studies demonstrating a dominant role for the paracellular pathway. The existence of phosphate sensing has been acknowledged for decades; however, the underlying molecular mechanisms are poorly understood. At least three phosphate sensors have emerged. PiT2 and FGFR1c both act as phosphate sensors controlling Fibroblast Growth Factor 23 secretion in bone, whereas the calcium-sensing receptor controls parathyroid hormone secretion in response to extracellular phosphate. All three of the proposed sensors are expressed in the kidney and intestine but their exact function in these organs is unknown. Understanding organ interactions and the mechanisms involved in phosphate sensing requires significant research to develop novel approaches for the treatment of phosphate homeostasis disorders.

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A putative cyclin, SiPHO80 from root endophytic fungus Serendipita indica regulates phosphate homeostasis, salinity and heavy metal toxicity tolerance

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2018.11.053 ◽

2018 ◽

Vol 507 (1-4) ◽

pp. 414-419

Author(s):

Anita Loha ◽

Arun Kumar Kashyap ◽

Pooja Sharma

Keyword(s):

Heavy Metal ◽

Endophytic Fungus ◽

Metal Toxicity ◽

Heavy Metal Toxicity ◽

Phosphate Homeostasis

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Effects of Dapagliflozin on Circulating Markers of Phosphate Homeostasis

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.04530418 ◽

2018 ◽

Vol 14 (1) ◽

pp. 66-73 ◽

Cited By ~ 24

Author(s):

Maarten A. de Jong ◽

Sergei I. Petrykiv ◽

Gozewijn D. Laverman ◽

Antonius E. van Herwaarden ◽

Dick de Zeeuw ◽

...

Keyword(s):

Kidney Disease ◽

Diabetic Kidney Disease ◽

Early Stage ◽

Glycosylated Hemoglobin ◽

Fibroblast Growth Factor 23 ◽

Serum Phosphate ◽

Phosphate Homeostasis ◽

Double Blind ◽

Diabetic Kidney ◽

Albumin Excretion

Background and objectivesThe sodium glucose cotransporter 2 (SGLT-2) inhibitor dapagliflozin is a novel drug for the treatment of diabetes mellitus. Recent studies suggest that SGLT-2 inhibitors affect phosphate homeostasis, but their effects on phosphate-regulating hormones in patients with diabetic kidney disease are still unclear.Design, setting, participants, & measurementsWe performed a post-hoc analysis of a double-blind, randomized, crossover trial in patients with type 2 diabetes with early-stage diabetic kidney disease on stable renin–angiotensin–aldosterone system blockade, with an albumin-to-creatinine ratio between 100 and 3500 mg/g, eGFR≥45 ml/min per 1.73 m2, and glycosylated hemoglobin≥7.2% and <11.4%. Patients were randomized to dapagliflozin 10 mg/d or placebo during consecutive 6-week study periods, separated by a 6-week wash-out. We investigated effects on circulating phosphate, calcium, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), 25-hydroxyvitamin D (25[OH]D), and 1,25-dihydroxyvitamin D (1,25[OH]2D) levels.ResultsThirty-one patients (age 62 years; 23% female) were analyzed. Compared with placebo, dapagliflozin increased serum phosphate by 9% (95% confidence interval, 4% to 15%; P=0.002), PTH increased by 16% (3% to 30%; P=0.01), FGF23 increased by 19% (0.3% to 42%; P=0.05), and serum 1,25(OH)2D decreased by −12% (−25% to 4%; P=0.12). Calcium and 25(OH)D were unaffected. We found no correlation between changes in markers of phosphate homeostasis and changes in eGFR or 24-hour albumin excretion during dapagliflozin treatment.ConclusionsDapagliflozin increases serum phosphate, plasma PTH, and FGF23. This effect was independent of concomitant changes in eGFR or 24-hour albumin excretion.

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