Vavrova, Katerina and Henkes, Dominika and Struever, Kay and Sochorova, Michaela and Skolova, Barbora and Witting, Madeleine Y. and Friess, Wolfgang and Schreml, Stephan and Meier, Robert J. and Schaefer-Korting, Monika and Fluhr, Joachim W. and Kuechler, Sarah (2014) Filaggrin Deficiency Leads to Impaired Lipid Profile and Altered Acidification Pathways in a 3D Skin Construct. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 134 (3). pp. 746-753. ISSN 0022-202X, 1523-1747
Full text not available from this repository. (Request a copy)Abstract
Mutations in the filaggrin (FLG) gene are strongly associated with common dermatological disorders such as atopic dermatitis. However, the exact underlying pathomechanism is still ambiguous. Here, we investigated the impact of FLG on skin lipid composition, organization, and skin acidification using a FLG knockdown (FLG) skin construct. Initially, sodium/hydrogen antiporter (NHE-1) activity was sufficient to maintain the acidic pH (5.5) of the reconstructed skin. At day 7, the FLG degradation products urocanic (UCA) and pyrrolidone-5-carboxylic acid (PCA) were significantly decreased in FLG - constructs, but the skin surface pH was still physiological owing to an upregulation of NHE-1. At day 14, secretory phospholipase A(2) (sPLA(2)) IIA, which converts phospholipids to fatty acids, was significantly more activated in FLG- than in FLG+. Although NHE-1 and sPLA(2) were able to compensate the FLG deficiency, maintain the skin surface pH, and ensured ceramide processing (no differences detected), an accumulation of free fatty acids (2-fold increase) led to less ordered intercellular lipid lamellae and higher permeability of the FLG constructs. The interplay of the UCA/PCA and the sPLA(2)/NHE-1 acidification pathways of the skin and the impact of FLG insufficiency on skin lipid composition and organization in reconstructed skin are described.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HUMAN STRATUM-CORNEUM; ATOPIC-DERMATITIS; BARRIER FUNCTION; PHASE-BEHAVIOR; FATTY-ACIDS; IN-VITRO; CERAMIDE; ORGANIZATION; ENZYME; EXPRESSION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Dermatologie und Venerologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Nov 2019 10:13 |
| Last Modified: | 21 Nov 2019 10:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/10627 |
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