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