Stimulation of PPARα normalizes the skin lipid ratio and improves the skin barrier of normal and filaggrin deficient reconstructed skin
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
26472199
DOI
10.1016/j.jdermsci.2015.09.012
PII: S0923-1811(15)30052-9
Knihovny.cz E-resources
- Keywords
- Filaggrin deficiency, PPAR agonists, Reconstructed skin models, Skin barrier recovery, Skin lipids,
- MeSH
- Time Factors MeSH
- Phenotype MeSH
- Fibroblasts drug effects metabolism MeSH
- Filaggrin Proteins MeSH
- Genotype MeSH
- Skin Absorption drug effects MeSH
- Cells, Cultured MeSH
- Skin drug effects metabolism MeSH
- Docosahexaenoic Acids pharmacology MeSH
- Fatty Acids, Nonesterified metabolism MeSH
- Humans MeSH
- Membrane Proteins genetics metabolism MeSH
- Lipid Metabolism drug effects MeSH
- Permeability MeSH
- PPAR alpha agonists metabolism MeSH
- PPAR gamma agonists metabolism MeSH
- Protein Precursors genetics metabolism MeSH
- Intermediate Filament Proteins deficiency genetics MeSH
- Pyrimidines pharmacology MeSH
- RNA Interference MeSH
- Signal Transduction drug effects MeSH
- Testosterone metabolism MeSH
- Thiazolidinediones pharmacology MeSH
- Transfection MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ciglitazone MeSH Browser
- Filaggrin Proteins MeSH
- FLG protein, human MeSH Browser
- involucrin MeSH Browser
- Docosahexaenoic Acids MeSH
- Fatty Acids, Nonesterified MeSH
- loricrin MeSH Browser
- Membrane Proteins MeSH
- pirinixic acid MeSH Browser
- PPAR alpha MeSH
- PPAR gamma MeSH
- Protein Precursors MeSH
- Intermediate Filament Proteins MeSH
- Pyrimidines MeSH
- Testosterone MeSH
- Thiazolidinediones MeSH
BACKGROUND: Therapeutic options for atopic dermatitis mostly address the symptoms but causal therapies are still missing. Peroxisome proliferator activated receptor (PPAR) agonists exert beneficial effects in patients suffering this disease, whereas the stimulation of PPARα and γ seemed most promising. OBJECTIVES: To elucidate the effects of the PPARα specific agonist WY14643, the PPARγ agonist ciglitazone, and the dual PPARα+γ agonist docosahexaenoic acid (DHA) on the homeostasis and barrier function of filaggrin deficient skin. METHODS: The effects of the PPAR agonists on skin differentiation were evaluated via qPCR, Western blot, histological or immunofluorescence staining. Skin lipid organization was determined by ATR-FTIR and lipid composition was analyzed by HPTLC. Ultimately, the skin barrier function was assessed by skin absorption studies using the radioactively labeled compound testosterone. RESULTS: Significant upregulation of filaggrin after DHA and WY14643 supplementation, but no effect of ciglitazone, on protein and mRNA level was detected. DHA and WY14643, but not ciglitazone, normalized the molar ratio of the main skin barrier lipids to 1:1:1 (free fatty acids:ceramides:cholesterol). Furthermore, DHA and WY14643 supplementation normalized the skin lipid profile in filaggrin deficient skin, but only WY14643 significantly improved the skin barrier function. CONCLUSION: Supplementation particularly with the PPARα agonist WY14643 improved the homeostasis and barrier function of filaggrin deficient skin models by normalization of the free fatty acid profile underlining the potential of PPAR agonists for the treatment of filaggrin-associated skin diseases.
Charles University Prague Faculty of Pharmacy Hradec Kralove Czech Republic
Institute for Pharmaceutical Sciences Pharmacology and Toxicology Freie Universität Berlin Germany
References provided by Crossref.org
Lysosphingolipids in ceramide-deficient skin lipid models
TSLP is a direct trigger for T cell migration in filaggrin-deficient skin equivalents
