Decreased mRNA levels of retinoic acid receptor alpha, retinoid X receptor alpha and thyroid hormone receptor alpha in lesional psoriatic skin.
Retinoic acid, vitamin D3 and triiodothyronine regulate keratinocyte proliferation and differentiation--processes that are disturbed in psoriatic skin--via binding to nuclear receptors for retinoic acid (RAR-alpha,-gamma), vitamin D3 (VDR), thyroid hormone (TR-alpha,-beta) plus the common heterodimer partners, the 9-cis-retinoic acid receptors (RXR-alpha,-beta). By using a new quantitative real-time polymerase chain reaction assay, the expression of these receptors and three housekeeping genes (cyclophilin, GAPDH and beta-actin) was studied in psoriatic skin. The expression of housekeeping genes was consistently 2.7-4.3 times higher in lesional than in non-lesional skin. When the beta-actin expression was used to normalize the receptor mRNA values, the RARalpha, RXRalpha and TRalpha transcripts were found to be 58-75% lower in lesional vs. non-lesional skin and the RXRalpha:RARgamma 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 normalize 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 how this relates to the pathogenesis of the disease is still unclear.
Törmä
H
H
Department of Medical Sciences, University of Uppsala, Sweden.
Karlsson
T
T
Michaëlsson
G
G
Rollman
O
O
Vahlquist
A
A
D002117:Calcitriol / Q000031:analogs & derivatives / Q000494:pharmacology; D003879:Dermatologic Agents / Q000494:pharmacology; D006801:Humans; D007641:Keratolytic Agents / Q000494:pharmacology; D011565:Psoriasis / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000187:drug effects; D018168:Receptors, Retinoic Acid / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000235:genetics*; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000235:genetics*; D014212:Tretinoin / Q000494:pharmacology
D003879:Dermatologic Agents; D007641:Keratolytic Agents; C000607071:RARA protein, human; D012333:RNA, Messenger; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D014157:Transcription Factors; C055085:calcipotriene; D014212:Tretinoin; D002117:Calcitriol