Mechanism of vitamin D₃-induced transcription of phospholipase D1 in HaCat human keratinocytes

1α,25-Dihydroxyvitamin D₃ (VitD₃) increases protein and gene expression of phospholipase D1 (PLD1), but not PLD2, in HaCaT human keratinocytes. We show that VitD₃ increases PLD1 gene expression through a vitamin D responsive element (VDRE) on the 5′ PLD1 promoter (-260 bp to -246 bp from exon 1). Similar results were obtained by transfecting VitD₃ receptor (VDR) into HEK293 cells, which are originally VitD₃-unresponsive. Electrophoresis mobility shift assays (EMSA) and chromatin immunoprecipitation (CHIP) assays showed that the complex of VitD₃, VDR and retinoid X receptor α (RXRα) binds to the VDRE and increases PLD1 gene expression in HaCaT cells.