Disturbed expression of vitamin D and retinoic acid-related orphan receptors and and of megalin in inflammatory skin diseases

The pathogenesis of inflammatory skin diseases is associated with the abnormal activity of keratinocytes and immune cells infiltrate. Vitamin D-3 deficiency can correlate with the increased incidence, severity and duration of inflammatory skin disorders. The exact mechanism on how vitamin D-3 influences inflammatory skin diseases still requires clarification. However, it can be associated with the disturbances in transmembrane glycoprotein-LRP2/megalin, which is implicated in vitamin D-3 transport to the cell, and defects in vitamin D-signalling through the nuclear receptors. Therefore, by using immunohistochemistry, we analysed the expression of LRP2/megalin, VDR, ROR alpha and ROR gamma in allergic contact dermatitis, lichen simplex chronicus, sarcoidosis and psoriasis in comparison with the normal skin. We observed decreased expression of LRP2/megalin in all inflammatory lesions in comparison with the normal skin. Significant differences were also noticed in VDR, ROR alpha and ROR gamma levels between inflammatory lesions and normal skin. Our research indicates disturbed expression of LRP2/megalin, VDR, ROR alpha and ROR gamma in inflammatory skin lesions in comparison with normal skin. Therefore, we suggest that changes in the activity of these proteins may play role in pathogenesis of inflammatory skin disorders. Furthermore, we suggest that LRP2/megalin, VDR, ROR alpha and RORy may serve as targets in therapy of these diseases.