Enhancing 1α-Hydroxylase Activity with the 25-Hydroxyvitamin D-1α-Hydroxylase Gene in Cultured Human Keratinocytes and Mouse Skin

The study investigated enhancing 1α-hydroxylase activity in human keratinocytes and mouse skin using the 25-hydroxyvitamin D-1α-hydroxylase gene to treat hyperproliferative skin disorders like psoriasis. Transfecting keratinocytes with a 1α-OHase-GFP plasmid increased 1α-OHase activity and sensitivity to 25(OH)D3's antiproliferative effects. Topical application on mice showed enhanced 1α-OHase expression in the skin, including hair follicles. This method could potentially treat skin disorders locally without causing hypercalcemia or drug resistance, by increasing local 1α,25(OH)2D3 production and normalizing cell proliferation and differentiation.