Details

Autor(en) / Beteiligte

• Pendaries, Valérie
• Malaisse, Jeremy
• Pellerin, Laurence
• Le Lamer, Marina
• Nachat, Rachida
• Kezic, Sanja
• Schmitt, Anne-Marie
• Paul, Carle
• Poumay, Yves
• Serre, Guy
• Simon, Michel

Titel

Knockdown of Filaggrin in a Three-Dimensional Reconstructed Human Epidermis Impairs Keratinocyte Differentiation

Ist Teil von

• Journal of investigative dermatology, 2014-12, Vol.134 (12), p.2938-2946

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2014

Link zum Volltext

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• Atopic dermatitis is a chronic inflammatory skin disorder characterized by defects in the epidermal barrier and keratinocyte differentiation. The expression of filaggrin, a protein thought to have a major role in the function of the epidermis, is downregulated. However, the impact of this deficiency on keratinocytes is not really known. This was investigated using lentivirus-mediated small-hairpin RNA interference in a three-dimensional reconstructed human epidermis (RHE) model, in the absence of other cell types than keratinocytes. Similar to what is known for atopic skin, the experimental filaggrin downregulation resulted in hypogranulosis, a disturbed corneocyte intracellular matrix, reduced amounts of natural moisturizing factor components, increased permeability and UV-B sensitivity of the RHE, and impaired keratinocyte differentiation at the messenger RNA and protein levels. In particular, the amounts of two filaggrin-related proteins and one protease involved in the degradation of filaggrin, bleomycin hydrolase, were lower. In addition, caspase-14 activation was reduced. These results demonstrate the importance of filaggrin for the stratum corneum properties/functions. They indicate that filaggrin downregulation in the epidermis of atopic patients, either acquired or innate, may be directly responsible for some of the disease-related alterations in the epidermal differentiation program and epidermal barrier function.