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Isolation and Culture of Primary Mouse Keratinocytes from Neonatal and Adult Mouse Skin
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Hypoxia-inducible factors regulate filaggrin expression and epidermal barrier function
Waihay J Wong1, Theresa Richardson2, John T Seykora3
1Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania, USA; Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
The Journal of Investigative Dermatology
|July 8, 2014
Summary
Hypoxia-inducible factors (HIFs) are crucial for skin barrier formation. Loss of HIFs impairs keratinocyte differentiation and reduces filaggrin, leading to a defective epidermal barrier.
Area of Science:
- Dermatology
- Molecular Biology
- Cell Biology
Background:
- A functional epidermal skin barrier is essential for protection.
- Keratinocyte terminal differentiation forms the cornified envelope.
- Genetic and environmental signals regulate skin barrier development.
Purpose of the Study:
- To investigate the role of hypoxia-inducible factors (HIFs) in epidermal skin barrier formation.
- To determine the impact of HIFs on filaggrin expression and keratinocyte differentiation.
Main Methods:
- Simultaneous deletion of Hif1a and Hif2a genes in murine epidermis.
- Analysis of epidermal barrier function, keratinocyte differentiation, and filaggrin expression.
- Hypoxic treatment of primary keratinocytes to assess gene expression.
Main Results:
- Mice lacking epidermal Hif1a and Hif2a showed impaired skin barrier function, dry flaky skin, and increased sensitivity to allergens.
- These defects were associated with reduced filaggrin expression and stratum granulosum attenuation.
- Hypoxia induced filaggrin gene expression in a HIF1α- and HIF2α-dependent manner in keratinocytes.
Conclusions:
- Hypoxia-inducible factors (HIFs) play a critical role in regulating epidermal differentiation and skin barrier integrity.
- Filaggrin expression is dependent on HIFs, and their loss leads to epidermal barrier defects.
- Low oxygen tension is an essential environmental factor for proper skin development and function.
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