Klf4 and corticosteroids activate an overlapping set of transcriptional targets to acceleratein uteroepidermal barrier acquisition
- 5 December 2006
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 103 (49) , 18668-18673
- https://doi.org/10.1073/pnas.0608658103
Abstract
Premature infants are at an increased risk for infections and dehydration because of incomplete development of the epidermis, which attains its essential function as a barrier only during the last stages ofin uterodevelopment. When a premature birth is anticipated, antenatal corticosteroids are administered to accelerate lung epithelium differentiation. One pleiotropic, but beneficial, effect of antenatal corticosteroids is acceleration of skin barrier establishment by an unknown mechanism. In mice, the transcription factor Klf4 is both necessary and sufficient, within a developmental field of competence, to establish this skin barrier, as demonstrated by targeted ablation and transgenic expression of Klf4, respectively. Here, we report that Klf4 and corticosteroid treatment coordinately accelerate barrier acquisitionin vivo. Transcriptional profiling reveals that the genes regulated by corticosteroids and Klf4 during the critical window of epidermal development significantly overlap. KLF4 activates the proximal promoters of a significant subset of these genes. Dissecting the intersection of the genetic and pharmacological pathways, regulated by KLF4 and corticosteroids, respectively, leads to a mechanistic understanding of the normal process of epidermal developmentin utero.Keywords
This publication has 43 references indexed in Scilit:
- Epidermal barrier formation and recovery in skin disordersJournal of Clinical Investigation, 2006
- Connexin 26 regulates epidermal barrier and wound remodeling and promotes psoriasiform responseJournal of Clinical Investigation, 2006
- Sequence and Haplotype Analysis Supports HLA-C as the Psoriasis Susceptibility 1 GeneAmerican Journal of Human Genetics, 2006
- Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitisNature Genetics, 2006
- Evolutionarily conserved elements in vertebrate, insect, worm, and yeast genomesGenome Research, 2005
- Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- miceGenes & Development, 2004
- Short-Term Glucocorticoid Treatment Compromises Both Permeability Barrier Homeostasis and Stratum Corneum Integrity: Inhibition of Epidermal Lipid Synthesis Accounts for Functional AbnormalitiesJournal of Investigative Dermatology, 2003
- Getting under the skin of epidermal morphogenesisNature Reviews Genetics, 2002
- Altered skin development and impaired proliferative and inflammatory responses in transgenic mice overexpressing the glucocorticoid receptorThe FASEB Journal, 2001
- Epidermal Barrier Ontogenesis: Maturation in Serum-Free Media and Acceleration by Glucocorticoids and Thyroid Hormone but Not Selected Growth FactorsJournal of Investigative Dermatology, 1996