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

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.