Single collection et king rar skin#
Single collection et king rar Activator#
Single collection et king rar rar#

Retinoid Receptor-specific Agonists and AntagonistsДЄTRA was a gift from BASF (Ludwigshafen, D) and the synthetic RXR activator LG268 was kindly provided by Ligand Pharmaceuticals (San Diego, CA).

Single collection et king rar skin#

This might allow for conclusions regarding the involvement of subtype-specific retinoid receptor-mediated signaling in various skin diseases and may suggest alternative therapeutic strategies.

The outcome of the present study will help to identify pathways and genes that are selectively regulated by RARО±, RARОі, or RXR in the skin of mice.

Single collection et king rar rar#

Our aim was to determine the effect of RAR subtype-selective and RXR activation or antagonism on the expression of genes involved in retinoid metabolism and signaling, as well as epidermal barrier homeostasis and skin-based immune regulation. In order to dissect retinoid-mediated signaling in skin, mice were treated topically for two weeks with selective RAR and RXR agonists or antagonists. Altered retinoid-mediated signaling in skin of these patients may also be a result of activation or antagonism of specific retinoid receptor subtypes under disease conditions.

However, alterations in retinoid metabolism, signaling and concentrations have been observed in various dermatoses, such as psoriasis, ichthyosis, and recently in a study by our group in atopic dermatitis. Retinoid metabolism and concentrations in skin are tightly regulated ensuring sufficient levels of the endogenous pan-RAR activator all- trans retinoic acid (ATRA). RAR-RXR-mediated signaling pathways induced by retinoids are essentially involved in immune-modulatory events вЂ“, and skin physiology through their role in the regulation of several aspects of skin cell proliferation, differentiation, apoptosis, and epidermal barrier function. Moreover, RAR and RXR subtypes differ in ligand specificity and/or affinity, вЂ“, therefore, it can be assumed that their contribution to gene expression patterns in skin differs, depending on quantitative receptor distribution, on the nature and level of co-regulators, as well as on available retinoid receptor-selective agonists and antagonists. Since retinoid receptors exhibit tissue and cell type-specific distribution patterns, functional specificity of each subtype is suggested вЂ“. The most abundant RAR and RXR subtypes in skin are RXRО± and RARОі, followed by lower quantities of RARО±. RAR-RXR heterodimers regulate the expression of multiple genes in skin and various other tissues, while their transcriptional activity is dependent on the RAR-activating ligand вЂ“. The nuclear hormone receptors retinoic acid receptors (RAR) О±, ОІ, and Оі and retinoid X receptors (RXR) О±, ОІ, and Оі are ligand-dependent transcription factors that can be activated by retinoids. We suggest that dysregulated retinoid signaling in the skin mediated by RXR, RARО± and/or RARОі may promote skin-based inflammation and dysregulation of skin barrier properties. Our results indicate that RARО± and RARОі subtypes possess different roles in the skin and may be of relevance for the auto-regulation of endogenous retinoid signaling in skin. In contrast, a RARО± 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. ATRA and the RARОі agonist further increased retinoid target gene expression (Rbp1, Crabp2, Krt4, Cyp26a1, Cyp26b1) and the chemokines Ccl17 and Ccl22. We observed pronounced epidermal hyperproliferation upon application of ATRA and synthetic agonists for RARОі and RXR. The present study used topical application of selective agonists and antagonists for retinoic acid receptors (RARs) О± and Оі 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. Moreover, retinoid signaling was found to be dysregulated in various skin diseases. Endogenous retinoids like all- trans retinoic acid (ATRA) play important roles in skin homeostasis and skin-based immune responses.

Single collection et-king rar