Decreased mRNA levels of retinoic acid receptor alpha, retinoid X receptoralpha and thyroid hormone receptor alpha in lesional psoriatic skin

Retinoic acid, vitamin DS and triiodothyronine regulate keratinocyte prolif eration and differentiation - processes that are disturbed in psoriatic ski n - via binding to nuclear receptors far retinoic acid (RAR-alpha,-gamma,), vitamin D-3 (VDR), thyroid hormone (TR-alpha,-beta) plus the common hetero dimer partners, the 9-cis-retinoic acid receptors (RXR-alpha,-beta), By usi ng a new quantitative real-time polymerase chain reaction assay, the expres sion of these receptors and three housekeeping genes (cyclophilin, GAPDH an d beta-actin) nas studied in psoriatic skin. The expression of housekeeping genes was consistently 2.7-4.3 times higher in lesional than in nonlesiona l skin, When the beta-actin expression was used to normalize the receptor m RNA values, the RAR alpha, RXR alpha and TR alpha transcripts were found to be 58-75% lower in lesional vs. non-lesional skin and the RXR alpha:RAR ga mma ratio was reduced from 3.2 to 1.5. Topical treatment for 4 days with 0. 025% all-trans-retinoic acid or calcipotriol under occlusion did not normal ize the altered mRNA expression of RARs, RXR and VDR in lesional skin. The results suggest that retinoid and thyroid hormone signalling is abnormal in lesional psoriatic skin, but holy this relates to the pathogenesis of the disease is still unclear.