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Título: | Glucocorticoid-dependent transcription in skin requires epidermal expression of the glucocorticoid receptor and is modulated by the mineralocorticoid receptor |
Autor: | Sevilla, Lisa M. CSIC ORCID; Bigas, Judit CSIC ORCID; Chiner-Oms, Álvaro CSIC ORCID ; Comas, Iñaki CSIC ORCID ; Sentandreu, Vicente; Pérez, Paloma CSIC ORCID | Fecha de publicación: | 3-nov-2020 | Editor: | Nature Publishing Group | Citación: | Scientific Reports 10(1):18954 (2020) | Resumen: | Glucocorticoid (GC) actions are mediated through two closely related ligand-dependent transcription factors, the GC receptor (GR) and the mineralocorticoid receptor (MR). Given the wide and effective use of GCs to combat skin inflammatory diseases, it is important to understand the relative contribution of these receptors to the transcriptional response to topical GCs. We evaluated the gene expression profiles in the skin of mice with epidermal-specific loss of GR (GREKO), MR (MREKO), or both (double KO; DKO) in response to dexamethasone (Dex). The overall transcriptional response was abolished in GREKO and DKO skin suggesting dependence of the underlying dermis on the presence of epidermal GR. Indeed, the observed dermal GC resistance correlated with a constitutive decrease in GR activity and up-regulation of p38 activity in this skin compartment. Upon Dex treatment, more than 90% of differentially expressed genes (DEGs) in CO overlapped with MREKO. However, the number of DEGs was fourfold increased and the magnitude of response was higher in MREKO vs CO, affecting both gene induction and repression. Taken together our data reveal that, in the cutaneous transcriptional response to GCs mediated through endogenous receptors, epidermal GR is mandatory while epidermal MR acts as a chief modulator of gene expression. | Descripción: | 11 págs., 6 figuras. All data generated or analyzed during this study are included in this published article (and its SupplementaryInformation fles) at https://doi.org/10.1038/s41598-020-75853-5. | Versión del editor: | http://dx.doi.org/10.1038/s41598-020-75853-5 | URI: | http://hdl.handle.net/10261/222384 | DOI: | 10.1038/s41598-020-75853-5 | E-ISSN: | 2045-2322 |
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2020 Sci Rep 10-18954.pdf | 3,65 MB | Adobe PDF | Visualizar/Abrir |
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