Regulation of a Novel Immediate Early Response Gene,IEX-1,in Keratinocytes by 1α,25-Dihydroxyvitamin D3

1α,25-Dihydroxyvitamin D3[1α,25(OH)2D3] regulates cellular growth and differentiation. We show that in keratinocytes, 1α,25(OH)2D3reduces concentrations of the messenger RNA ofIEX-1,the product of which blocks Fas- or tumor necrosis factor type α-induced apoptosis in various cells. In sub-confluent keratinocyte cultures, the addition of 1α,25(OH)2D3, in amounts that induce growth arrest, reducesIEX-1mRNA concentrations. In confluent cells, 1α,25(OH)2D3initially reduces and then increasesIEX-1mRNA concentrations. IEX-1 protein is localized in the nucleus and perinuclear region of keratinocytes. In sub-confluent cells, 1α,25(OH)2D3translocates IEX-1 protein from the nucleus to the perinuclear region and cytoplasm. Since IEX-1 has recently been shown to regulate cell survival and number, we suggest thatIEX-1may play a role in keratinocyte growth and differentiation and that 1α,25(OH)2D3may reduce keratinocyte growth via a reduction inIEX-1mRNA and a change in the intracellular distribution of IEX-1 protein.