title: Regulation of retinoid-mediated signaling involved in skin homeostasis by RAR and RXR agonists/antagonists in mouse skin.
abstract: Endogenous retinoids like all-trans retinoic acid (ATRA) play important roles in skin homeostasis and skin-based immune responses. Moreover, retinoid signaling was found to be dysregulated in various skin diseases. The present study used topical application of selective agonists and antagonists for retinoic acid receptors (RARs) α and γ and retinoid-X receptors (RXRs) for two weeks on mouse skin in order to determine the role of retinoid receptor subtypes in the gene regulation in skin. We observed pronounced epidermal hyperproliferation upon application of ATRA and synthetic agonists for RARγ and RXR. ATRA and the RARγ agonist further increased retinoid target gene expression (Rbp1, Crabp2, Krt4, Cyp26a1, Cyp26b1) and the chemokines Ccl17 and Ccl22. In contrast, a RARα agonist strongly decreased the expression of ATRA-synthesis enzymes, of retinoid target genes, markers of skin homeostasis, and various cytokines in the skin, thereby markedly resembling the expression profile induced by RXR and RAR antagonists. Our results indicate that RARα and RARγ subtypes possess different roles in the skin and may be of relevance for the auto-regulation of endogenous retinoid signaling in skin. We suggest that dysregulated retinoid signaling in the skin mediated by RXR, RARα and/or RARγ may promote skin-based inflammation and dysregulation of skin barrier properties.
authors: Department of Biochemistry and Molecular Biology, University of Debrecen, Debrecen, Hungary.
authors: Janine
authors: J
authors: Gericke
authors: Jan
authors: J
authors: Ittensohn
authors: Johanna
authors: J
authors: Mihály
authors: Susana
authors: S
authors: Alvarez
authors: Rosana
authors: R
authors: Alvarez
authors: Dániel
authors: D
authors: Töröcsik
authors: Angel R
authors: AR
authors: de Lera
authors: Ralph
authors: R
authors: Rühl
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D004817:Epidermis / Q000187:drug effects / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects / Q000276:immunology; D051379:Mice; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012176:Retinoids / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology; D000097768:Retinoic Acid Receptor gamma
chemical_list: D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D047488:Retinoid X Receptors; D012176:Retinoids; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C000607072:Rara protein, mouse
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