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Título: | Identification of novel glucocorticoid receptor-regulated genes involved in epidermal homeostasis and hair follicle differentiation |
Autor: | Donet, Eva CSIC; Bayo, Pilar CSIC; Calvo, Ezequiel Luis; Labrie, Fernand; Pérez, Paloma CSIC ORCID | Palabras clave: | glucocorticoid receptor epidermal homeostasis microarray analysis transgenic mice |
Fecha de publicación: | 7-sep-2007 | Editor: | Elsevier | Citación: | The Journal of Steroid Biochemistry and Molecular Biology 108 (1-2): 8-16 (2008) | Resumen: | Despite that glucocorticoids (GCs), acting through the glucocorticoid receptor (GR) exert a pivotal role in skin physiopathology, specific genes regulated by GR in this tissue are largely unknown. We have used a transgenic mouse model overexpressing GR in epidermal basal cells and outer root sheath (ORS) of the hair follicle (HF) under the control of the keratin 5 regulatory sequences (K5-GR mice) to identify GR-regulated genes in mouse skin. We analyzed the transcriptomic profile of adult K5-GR skin as compared to non-transgenic adult mice by using oligonucleotide microarrays and identified 173 genes differentially regulated by GR in this tissue. Our data were further validated by semiquantitative RT-PCR and quantitative real-time PCR. We have identified a large subset of hair keratin intermediate filament (krt) and hair keratin-associated protein (krtap) genes, as well as several hox genes as GC-regulated. Since dysregulation of krt, krtaps and hox genes can cause hair disorders, as it occurs in adult K5-GR mice, our findings strongly suggest a role of GR in HF morphogenesis through the coordinated regulation of these hair-specific genes. In addition, we found that GR repressed several genes related to cell growth, such as the immediate early genes fosb and c-fos, according to the antiproliferative role described for this hormone receptor. By using cultured keratinocytes treated with GR-agonists and -antagonists, we demonstrated that down-regulation of fosb is mediated by GR. Identification of novel GR-regulated genes will help us to better understand the role of GCs as physiological modulators and pharmacological agents. | Descripción: | 9 pages, 3 figures PMID: 17935973 [PubMed] | Versión del editor: | http://dx.doi.org/10.1016/j.jsbmb.2007.05.033 | URI: | http://hdl.handle.net/10261/11921 | DOI: | 10.1016/j.jsbmb.2007.05.033 | ISSN: | 0960-0760 |
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Donet JSBMB 07.pdf | 2,19 MB | Adobe PDF | Visualizar/Abrir |
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