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

Arch Biochem Biophys. 2008 Sep 1;477(1):33-42. doi: 10.1016/j.abb.2008.06.006. Epub 2008 Jun 19.

Abstract

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-1alpha-hydroxylase (CYP27B1) in response to 50 nM of parathyroid hormone (PTH) and changes in extracellular calcium (Ca(2+)) 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 Ca(2+) 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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism*
  • Animals
  • Blotting, Western
  • Cell Line
  • Immunohistochemistry
  • Kidney Tubules, Distal / cytology
  • Kidney Tubules, Distal / enzymology
  • Kidney Tubules, Distal / metabolism*
  • Kidney Tubules, Proximal / cytology
  • Kidney Tubules, Proximal / enzymology
  • Kidney Tubules, Proximal / metabolism*
  • Mice
  • Promoter Regions, Genetic
  • Receptor, Parathyroid Hormone, Type 1 / metabolism
  • Receptors, Calcitriol / metabolism*
  • Receptors, Calcium-Sensing / metabolism
  • Steroid Hydroxylases / metabolism
  • Vitamin D3 24-Hydroxylase

Substances

  • Receptor, Parathyroid Hormone, Type 1
  • Receptors, Calcitriol
  • Receptors, Calcium-Sensing
  • Steroid Hydroxylases
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase