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1 Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Montreal Children's Hospital Research Institute, McGill University, Montreal, Quebec, Canada
2 Department of Medicine, McGill University, Montreal, Quebec, Canada
3 Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Department of Medicine, McGill University, Montreal, Quebec, Canada; Department of Physiology, McGill University, Montreal, Quebec, Canada
4 Department of Human Genetics, McGill University, Montreal, Quebec, Canada; Department of Pediatrics, McGill University, Montreal, Quebec, Canada; Montreal Children's Hospital Research Institute, McGill University, Montreal, Quebec, Canada
* To whom correspondence should be addressed. E-mail: harriet.tenenhouse{at}mcgill.ca.
Mutations in the PHEX gene are responsible for X-linked hypophosphatemia, a renal phosphate wasting disorder associated with defective skeletal mineralization. PHEX is predominantly expressed in bones and teeth and in the parathyroid gland of patients with chronic renal failure and tertiary hyperparathyroidism. The aim of the present study was to examine the effects of renal insufficiency and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) on the regulation of PHEX expression in rat tibia and parathyroid gland. In rats fed a high phosphate (Pi) diet, 5/6 nephrectomy elicited a significant increase in the serum PTH concentration that was associated with a significant increase in the abundance of PHEX mRNA and protein in tibia and a significant increase in PHEX mRNA in the parathyroid gland. In contrast, 1,25(OH)2D3 administration in intact rats fed a control diet elicited a significant decrease in the serum PTH concentration that was accompanied by a significant decrease in PHEX mRNA and protein abundance in tibia and a significant decrease in PHEX mRNA in the parathyroid gland. In addition, the increases in serum PTH levels and PHEX mRNA in tibia and parathyroid gland in 5/6 nephrectomized rats fed a high Pi diet were blunted by 1,25(OH)2D3. Serum PTH concentration was positively and significantly correlated with tibial PHEX mRNA and protein abundance. In summary, we demonstrate that PHEX expression in tibia and parathyroid gland is increased by chronic renal insufficiency and decreased by 1,25(OH)2D3 administration and suggest that PTH status may play an important role in mediating these changes in PHEX expression.
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  E. R. Hines, O. I. Kolek, M. D. Jones, S. H. Serey, N. B. Sirjani, P. R. Kiela, P. W. Jurutka, M. R. Haussler, J. F. Collins, and F. K. Ghishan 1,25-Dihydroxyvitamin D3 Down-regulation of PHEX Gene Expression Is Mediated by Apparent Repression of a 110 kDa Transfactor That Binds to a Polyadenine Element in the Promoter J. Biol. Chem., November 5, 2004; 279(45): 46406 - 46414. [Abstract] [Full Text] [PDF]
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