Extracellular calcium is a direct effecter of VDR levels in proximal tubule epithelial cells that counter-balances effects of PTH on renal Vitamin D metabolism.
In renal proximal tubules, VDR is transiently decreased by parathyroid hormone (PTH) during times of hypocalcemia and returns to normal levels with the rise in serum calcium (Ca). In this study we tested the hypothesis that elevated extracellular Ca induces VDR in a human renal proximal cell line (HK-2G) stably expressing PTH receptor type I. Exposure of HK-2G cells to increasing Ca concentration, up to 3mM, induced the expression of VDR. The increase in VDR occurred within 1h and was sustained over 24h. The increase in VDR was also dose-dependently increased using 20-100 nM gadolinium, suggesting the induction of VDR is regulated via the extracellular Ca sensing receptor (CaSR) with is naturally expressed in HK-2G cells. In conclusion, an extracellular Ca concentration in the physiological range is capable of direct increase of renal proximal VDR expression, and the induction mechanism represents a strategy the body may use to counterbalance effects of PTH on renal Vitamin D metabolism.
Maiti
Aparna
A
VCU School of Medicine, Department of Biochemistry, Orthopaedic Research Laboratory, 1112 E. Clay Street, Richmond, VA 23298-0614, USA.
Beckman
Matthew J
MJ
D002118:Calcium / Q000494:pharmacology*; D002460:Cell Line; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005682:Gadolinium / Q000494:pharmacology; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044168:Receptor, Parathyroid Hormone, Type 1 / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000378:metabolism*; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000378:metabolism; D013997:Time Factors; D014807:Vitamin D / Q000378:metabolism*
C473449:PTH1R protein, human; D010281:Parathyroid Hormone; D044168:Receptor, Parathyroid Hormone, Type 1; D018167:Receptors, Calcitriol; D044169:Receptors, Calcium-Sensing; D014807:Vitamin D; D005682:Gadolinium; D002118:Calcium