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1,25-Dihydroxyvitamin D (1,25(OH)(2)D) plays a critical role in calcium and phosphorus (Pi) metabolism, bone growth, and tissue differentiation. The synthesis of 1,25(OH)(2)D in the proximal renal tubule is the primary determinant of its circulating concentration and is mediated by the mitochondrial enzyme, 25-hydroxyvitamin D-1α-hydroxylase, CYP27B1).(More)
BACKGROUND AND OBJECTIVES Plasma fibroblast growth factor 23 (FGF23) concentrations increase early in the course of CKD in children. High FGF23 levels associate with progression of CKD in adults. Whether FGF23 predicts CKD progression in children is unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We tested the hypothesis that high plasma FGF23 is(More)
Fibroblast growth factor-23 (FGF-23) is a novel circulating peptide that regulates phosphorus (Pi) and vitamin D metabolism, but the mechanisms by which circulating FGF-23 itself is regulated are unknown. To determine whether the serum FGF-23 concentration is regulated by dietary intake of Pi, we fed wild-type (WT), Npt2a gene-ablated (Npt2a(-/-)), and Hyp(More)
Fibroblast growth factor-23 (FGF-23) is critical to the pathogenesis of a distinct group of renal phosphate wasting disorders: tumor-induced osteomalacia, X-linked hypophosphatemia, and autosomal dominant and autosomal recessive hypophosphatemic rickets. Excess circulating FGF-23 is responsible for their major phenotypic features which include(More)
CONTEXT Vitamin D 1alpha-hydroxylase deficiency, also known as vitamin D-dependent rickets type 1, is an autosomal recessive disorder characterized by the early onset of rickets with hypocalcemia and is caused by mutations of the 25-hydroxyvitamin D 1alpha-hydroxylase (1alpha-hydroxylase, CYP27B1) gene. The human gene encoding the 1alpha-hydroxylase is 5 kb(More)
The X-linked hypophosphatemic (Hyp) mouse carries a loss-of-function mutation in the phex gene and is characterized by hypophosphatemia due to renal phosphate (Pi) wasting, inappropriately suppressed 1,25-dihydroxyvitamin D [1,25(OH)₂D] production, and rachitic bone disease. Increased serum fibroblast growth factor-23 concentration is responsible for the(More)
In X-linked hypophosphatemia (XLH) and in its murine homologue, the Hyp mouse, increased circulating concentrations of fibroblast growth factor 23 (FGF-23) are critical to the pathogenesis of disordered metabolism of phosphate (P(i)) and 1,25-dihydroxyvitamin D [1,25(OH)(2)D]. In this study, we hypothesized that in Hyp mice, FGF-23-mediated suppression of(More)
The mitochondrial enzyme 25-hydroxyvitamin D 1α-hydroxylase, which is encoded by the CYP27B1 gene, converts 25OHD to the biological active form of vitamin D, 1,25-dihydroxyvitamin D (1,25(OH)2D). Renal 1α-hydroxylase activity is the principal determinant of the circulating 1,25(OH)2D concentration and enzyme activity is tightly regulated by several factors.(More)
Context: Vitamin D 1␣-hydroxylase deficiency, also known as vitamin D-dependent rickets type 1, is an autosomal recessive disorder characterized by the early onset of rickets with hypocalcemia and is caused by mutations of the 25-hydroxyvitamin D 1␣-hydroxylase (1␣-hydroxylase, CYP27B1) gene. The human gene encoding the 1␣-hy-droxylase is 5 kb in length,(More)
Fibroblast growth factor 23 (FGF23) is a potent regulator of phosphate (Pi) and vitamin D homeostasis. The transcription factor, early growth response 1 (egr-1), is a biomarker for FGF23-induced activation of the ERK1/2 signaling pathway. We have shown that ERK1/2 signaling blockade suppresses renal egr-1 gene expression and prevents FGF23-induced(More)
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