Specific regulation of CYP27B1 and VDR in proximal versus distal renal cells

In this study, we utilized murine renal proximal (MPCT-G) and distal (DKC-8) tubular epithelial cell lines to compare the gene expressions and promoter activities of 1,25(OH)(2)D-3 receptor (VDR) and 25-hydroxyvitamin D-1 alpha-hydroxylase (CYP27B1) in response to 50 nM of parathyroid hormone (PTH) and changes in extracellular calcium (Ca2+) concentration. In MPCT-G cells, VDR gene expression was suppressed by PTH, whereas CYP27B1 gene expression was elevated in response to PTH. In DKC-8 cells, treatment of PTH significantly increased the relative gene expression of VDR by 6.5-fold while CYP27B1 gene expression was unchanged. High Ca2+ exposure stimulated VDR gene expression and repressed CYP27B1 gene expression in both dose and time-dependent fashion in MPCT-G but not DKC-8 cells. The analysis of promoter activities and VDR protein levels corresponded with the gene expression data. We conclude that PTH-mediated decrease in VDR and increase in renal CYP27B1 is proximal cell-specific. (c) 2008 Elsevier Inc. All rights reserved.