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Identification of novel glucocorticoid receptor-regulated genes involved in epidermal homeostasis and hair follicle differentiation

AuthorsDonet, Eva; Bayo, Pilar ; Calvo, Ezequiel; Labrie, Fernand; Pérez, Paloma
Keywordsglucocorticoid receptor
epidermal homeostasis
microarray analysis
transgenic mice
Issue Date7-Sep-2007
CitationThe Journal of Steroid Biochemistry and Molecular Biology 108 (1-2): 8-16 (2008)
AbstractDespite 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.
Description9 pages, 3 figures PMID: 17935973 [PubMed]
Publisher version (URL)http://dx.doi.org/10.1016/j.jsbmb.2007.05.033
Appears in Collections:(IBV) Artículos
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