English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/149442
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:


Glucocorticoid receptor regulates overlapping and differential gene subsets in developing and adult skin

AuthorsSevilla, Lisa M. ; Bayo, Pilar ; Latorre, Víctor; Sanchis, Ana ; Pérez, Paloma
KeywordsGlucocorticoid receptor
Transcriptional regulation
Skin development
Issue Date29-Sep-2010
PublisherEndocrine Society
CitationMolecular Endocrinology ;24(11):2166-78 (2010)
AbstractWe have previously shown that the glucocorticoid receptor (GR) is required for skin homeostasis and epidermal barrier competence. To understand the transcriptional program by which GR regulates skin development, we performed a microarray analysis using the skin of GR(-/-) and GR(+/+) mice of embryonic d 18.5 and identified 442 differentially expressed genes. Functional clustering demonstrated overrepresentation of genes involved in ectoderm/epidermis development. We found strong repression of genes encoding proteins associated with the later stages of epidermal differentiation, such as several small proline-rich proteins (Sprrs) and corneodesmosin (Cdsn). This, together with the up-regulation of genes induced earlier during epidermal development, including the epithelial-specific gene transcripts E74-like factor 5 (Elf5) and keratin 77 (Krt77), fits with the phenotype of defective epidermal differentiation observed in the GR(-/-) mice. We also found down-regulation of the antimicrobial peptide defensin β 1 (Defb1) and FK506-binding protein 51 (Fkbp51). Skin developmental expression profiling of these genes and studies in cultured keratinocytes from GR(-/-) and wild type embryos demonstrated that gene regulation occurred in a cell-autonomous manner. To investigate the consequences of GR loss in adult epidermis, we generated mice with inducible inactivation of GR restricted to keratinocytes (K14-cre-ER(T2)//GR(loxP/loxP) mice). K14-cre-ER(T2)//GR(loxP/loxP) mice featured thickened skin with increased keratinocyte proliferation and impaired differentiation. Whereas Krt77 and Elf5 expression remained unaffected by loss of GR in adult epidermis, Fkbp51, Sprr2d, and Defb1 were strongly repressed. Importantly, we have identified both Fkbp51 and Defb1 as direct transcriptional targets of GR, and we have shown that GR-mediated regulation of these genes occurs in both developing and adult epidermis. We conclude that both overlapping and differential GR targets are regulated in developing vs. adult skin.
Description13 páginas, 6 figuras.
Publisher version (URL)http://dx.doi.org/10.1210/me.2010-0183
Appears in Collections:(IBV) Artículos
Files in This Item:
File Description SizeFormat 
2010 Mol Endocrinol 24-2166 auth vers.pdf339,91 kBAdobe PDFThumbnail
Show full item record
Review this work

Related articles:

WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.