Gene profiling the effects of calcium deficiency versus 1,25-dihydroxyvitamin D induced hypercalcemia in rat kidney cortex.
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.
Bajwa
A
A
Department of Biochemistry, Virginia Commonwealth University Medical Center, Richmond, 23298-0694, USA.
Horst
R L
RL
Beckman
M J
MJ
D000821:Animal Feed; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D002118:Calcium / Q000172:deficiency* / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation; D006934:Hypercalcemia / Q000378:metabolism*; D006996:Hypocalcemia / Q000378:metabolism; D007668:Kidney / Q000378:metabolism; D007672:Kidney Cortex / Q000378:metabolism*; D007684:Kidney Tubules / Q000378:metabolism; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000378:metabolism; D051381:Rats; D018167:Receptors, Calcitriol / Q000378:metabolism; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D050608:Sodium-Phosphate Cotransporter Proteins; D013250:Steroid Hydroxylases / Q000378:metabolism; D027981:Symporters / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D015854:Up-Regulation; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D018167:Receptors, Calcitriol; D017468:Receptors, Fibroblast Growth Factor; D050608:Sodium-Phosphate Cotransporter Proteins; D027981:Symporters; D014807:Vitamin D; D012313:RNA; C097949:1,25-dihydroxyvitamin D; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; C406322:vitamin D 1-alpha hydroxylase; D065668:Vitamin D3 24-Hydroxylase; D002118:Calcium