Characterization of Vitamin D-mediated induction of the CYP 24 transcription.

摘要

Transcription of the CYP24 (25-hydroxyvitamin D(3)-24-hydroxylase) gene is known to be induced by 1alpha,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3)). We studied the induction kinetics in detail in human skin-derived fibroblasts. While the basal transcription of this gene was very low, addition of 1,25(OH)(2)D(3) increased the mRNA level by 50-fold within 1h. The induction reached as high as 20000-fold after 12h. DNA microarray analysis also indicated that the induction ratio of the CYP24 gene is exceptionally high among 3800 human genes examined. The increase of mRNA was caused by stimulation of the transcription, but not by stabilization of mRNA. 24(R),25-dihydroxyvitamin D(3) (24,25(OH)(2)D(3)), a compound metabolically related to 1,25(OH)(2)D(3), also stimulated the CYP24 gene transcription, though at much higher concentrations. However, this stimulation was significantly augmented by synergistic actions of 24,25(OH)(2)D(3) and 1,25(OH)(2)D(3), suggesting that 24,25(OH)(2)D(3) or its metabolites might be playing some roles in the regulation of CYP24 gene transcription.