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Cultivating a Three-dimensional Reconstructed Human Epidermis at a Large Scale
Published on: May 28, 2021
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In a three-dimensional reconstructed human epidermis filaggrin-2 is essential for proper cornification
V Pendaries1, M Le Lamer1, L Cau1
11] UMR5165 CNRS, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [2] U1056 INSERM, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France [3] University of Toulouse, CHU Purpan, Place du Dr Baylac TSA40031, 31059 Toulouse CEDEX 9, France.
Cell Death & Disease
|February 20, 2015
Summary
Filaggrin-2 (FLG2) deficiency impairs skin barrier function, causing atopic dermatitis symptoms. Reduced FLG2 impacts cornification and stratum corneum integrity, highlighting its role in skin health.
Area of Science:
- Dermatology
- Molecular Biology
- Genetics
Background:
- Atopic dermatitis is a chronic inflammatory skin condition characterized by epidermal barrier defects.
- A FLG2 nonsense mutation is linked to atopic dermatitis in African-American children.
- Reduced filaggrin-2 (FLG2) expression is observed in European patients with atopic dermatitis.
Purpose of the Study:
- To elucidate the function of filaggrin-2 (FLG2) in epidermal homeostasis.
- To investigate the consequences of FLG2 deficiency on skin barrier properties.
- To evaluate the role of FLG2 in the pathogenesis of atopic dermatitis.
Main Methods:
- Downregulation of FLG2 expression using lentivirus-mediated shRNA interference.
- Utilized a three-dimensional reconstructed human epidermis (RHE) model.
- Assessed epidermal structure, pH, free amino acid levels, differentiation markers, and protein processing.
Main Results:
- FLG2 downregulation induced parakeratosis and a compact stratum corneum.
- Observed increased RHE surface pH and reduced free amino acids, leading to heightened UVB sensitivity.
- Decreased proteolytic processing of corneodesmosin, hornerin, and filaggrin, with reduced caspase-14 and bleomycin hydrolase levels.
Conclusions:
- Filaggrin-2 (FLG2) is crucial for proper cornification and a functional stratum corneum.
- FLG2 deficiency contributes to epidermal impairment observed in atopic dermatitis.
- Reduced FLG2 expression may be a key factor in atopic dermatitis pathogenesis.
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