Hypoxia-Inducible Factors Regulate Filaggrin Expression and Epidermal Barrier Function
| Autor: | Theresa Richardson, George Cotsarelis, Waihay J. Wong, M. Celeste Simon, John T. Seykora |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Keratinocytes
Stratum granulosum Dermatology Filaggrin Proteins Biology Biochemistry Permeability Article Cornified envelope Mice 03 medical and health sciences 0302 clinical medicine Intermediate Filament Proteins Gene expression Basic Helix-Loop-Helix Transcription Factors medicine Animals Promoter Regions Genetic Molecular Biology Cells Cultured 030304 developmental biology Regulation of gene expression 0303 health sciences integumentary system Epidermis (botany) Aryl Hydrocarbon Receptor Nuclear Translocator Cell Biology Hypoxia-Inducible Factor 1 alpha Subunit Cell biology medicine.anatomical_structure Gene Expression Regulation Hypoxia-inducible factors 030220 oncology & carcinogenesis Immunology Epidermis Keratinocyte Filaggrin |
| Zdroj: | The Journal of investigative dermatology |
| ISSN: | 0022-202X |
| DOI: | 10.1038/jid.2014.283 |
| Popis: | A functional epidermal skin barrier requires the formation of a cornified envelope from terminally differentiating keratinocytes. During this process, multiple genetic and environmental signals coordinately regulate protein expression and tissue differentiation. Here we describe a critical role for hypoxia-inducible factors (HIFs) in the regulation of filaggrin expression and skin barrier formation. Similar to other mammalian tissues, fetal epidermis in mice is normally O2 deprived. Simultaneous deletion of Hif1a and Hif2a in murine epidermis revealed defects in keratinocyte terminal differentiation and epidermal barrier formation. Mice lacking Hif1a and Hif2a in the epidermis exhibited dry flaky skin, impaired permeability barrier, and enhanced sensitivity to cutaneous allergens. These defects were correlated with stratum granulosum attenuation and reduced filaggrin expression. Hypoxic treatment of primary keratinocytes induced filaggrin (Flg) gene expression in a HIF1α- and HIF2α-dependent manner, suggesting that one mechanism by which Hif1a and Hif2a loss causes epidermal barrier defects in mice lies in Flg dysregulation. Therefore, low O2 tension is an essential component of the epidermal environment that contributes to skin development and function. |
| Databáze: | OpenAIRE |
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