Gene profiling the effects of calcium deficiency versus 1,25-dihydroxyvitamin D induced hypercalcemia in rat kidney cortex

Arch Biochem Biophys. 2005 Jun 15;438(2):182-94. doi: 10.1016/j.abb.2005.04.016.

Abstract

Determinants involved in the activation and repression of 1,25-dihydroxyvitamin D (1,25(OH)(2)D(3)) synthesis in renal cortex by changes in extracellular Ca were studied. Cortical kidney RNA isolated from hypocalcemic (LC) rats generated by a low Ca diet, and hypercalcemic (HC) rats generated by a normal Ca diet and two sequential 1 microg doses of 1,25(OH)(2)D(3). Among the genes up-regulated were 1alpha-OHase (4.6-fold) in the LC group and high differential gene expression of VDR (4.0-fold) and 24-OHase (10.4-fold) in the HC group. Moreover, the exposure of renal cortex to LC versus HC conditions revealed a high differential expression of a PKA-dominated pathway involving CBP interacting protein, GATA-1 and CREB transcription factors in the LC model. In the HC model, elevated renal cortex gene expression of several growth factors, peptide receptors, and intracellular signaling molecules depicts a role for CaSR activation and receptor tyrosine kinase signaling in 1,25(OH)(2)D(3)-mediated gene activation and repression of 1alpha-OHase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animal Feed
  • Animal Nutritional Physiological Phenomena
  • Animals
  • Calcium / deficiency*
  • Calcium / metabolism
  • Cytochrome P-450 Enzyme System / metabolism
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation
  • Hypercalcemia / metabolism*
  • Hypocalcemia / metabolism
  • Kidney / metabolism
  • Kidney Cortex / metabolism*
  • Kidney Tubules / metabolism
  • Models, Biological
  • Oligonucleotide Array Sequence Analysis
  • RNA / metabolism
  • Rats
  • Receptors, Calcitriol / metabolism
  • Receptors, Fibroblast Growth Factor / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Sodium-Phosphate Cotransporter Proteins
  • Steroid Hydroxylases / metabolism
  • Symporters / metabolism
  • Transcriptional Activation
  • Transfection
  • Up-Regulation
  • Vitamin D / analogs & derivatives*
  • Vitamin D / metabolism*
  • Vitamin D3 24-Hydroxylase

Substances

  • Receptors, Calcitriol
  • Receptors, Fibroblast Growth Factor
  • Sodium-Phosphate Cotransporter Proteins
  • Symporters
  • Vitamin D
  • RNA
  • 1,25-dihydroxyvitamin D
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • vitamin D 1-alpha hydroxylase
  • Vitamin D3 24-Hydroxylase
  • Calcium