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)2D3) 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 μg doses of 1,25(OH)2D3. Among the genes up-regulated were 1α-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)2D3-mediated gene activation and repression of 1α-OHase.