Regulation of Retinoid-Mediated Signaling Involved in Skin Homeostasis by RAR and RXR Agonists/Antagonists in Mouse Skin

Janine Gericke, Jan Ittensohn, Johanna Mihály, Susana Álvarez, Rosana Álvarez, D. Törőcsik, Ángel R. de Lera, Ralph Rühl

Research output: Contribution to journalArticle

23 Citations (Scopus)

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.

Original languageEnglish
Article numbere62643
JournalPLoS One
Volume8
Issue number4
DOIs
Publication statusPublished - Apr 24 2013

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Retinoid X Receptors
Retinoic Acid Receptors
retinoids
retinoic acid
Retinoids
agonists
antagonists
homeostasis
Skin
Homeostasis
receptors
mice
Tretinoin
Gene expression
autoregulation
Chemokines
Skin Diseases
Genes
topical application
skin diseases

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Regulation of Retinoid-Mediated Signaling Involved in Skin Homeostasis by RAR and RXR Agonists/Antagonists in Mouse Skin. / Gericke, Janine; Ittensohn, Jan; Mihály, Johanna; Álvarez, Susana; Álvarez, Rosana; Törőcsik, D.; de Lera, Ángel R.; Rühl, Ralph.

In: PLoS One, Vol. 8, No. 4, e62643, 24.04.2013.

Research output: Contribution to journalArticle

Gericke, Janine ; Ittensohn, Jan ; Mihály, Johanna ; Álvarez, Susana ; Álvarez, Rosana ; Törőcsik, D. ; de Lera, Ángel R. ; Rühl, Ralph. / Regulation of Retinoid-Mediated Signaling Involved in Skin Homeostasis by RAR and RXR Agonists/Antagonists in Mouse Skin. In: PLoS One. 2013 ; Vol. 8, No. 4.
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