Stimulation of PPARα normalizes the skin lipid ratio and improves the skin barrier of normal and filaggrin deficient reconstructed skin
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
26472199
DOI
10.1016/j.jdermsci.2015.09.012
PII: S0923-1811(15)30052-9
Knihovny.cz E-zdroje
- Klíčová slova
- Filaggrin deficiency, PPAR agonists, Reconstructed skin models, Skin barrier recovery, Skin lipids,
- MeSH
- časové faktory MeSH
- fenotyp MeSH
- fibroblasty účinky léků metabolismus MeSH
- filagriny MeSH
- genotyp MeSH
- kožní absorpce účinky léků MeSH
- kultivované buňky MeSH
- kůže účinky léků metabolismus MeSH
- kyseliny dokosahexaenové farmakologie MeSH
- kyseliny mastné neesterifikované metabolismus MeSH
- lidé MeSH
- membránové proteiny genetika metabolismus MeSH
- metabolismus lipidů účinky léků MeSH
- permeabilita MeSH
- PPAR alfa agonisté metabolismus MeSH
- PPAR gama agonisté metabolismus MeSH
- proteinové prekurzory genetika metabolismus MeSH
- proteiny intermediálních filament nedostatek genetika MeSH
- pyrimidiny farmakologie MeSH
- RNA interference MeSH
- signální transdukce účinky léků MeSH
- testosteron metabolismus MeSH
- thiazolidindiony farmakologie MeSH
- transfekce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ciglitazone MeSH Prohlížeč
- filagriny MeSH
- FLG protein, human MeSH Prohlížeč
- involucrin MeSH Prohlížeč
- kyseliny dokosahexaenové MeSH
- kyseliny mastné neesterifikované MeSH
- loricrin MeSH Prohlížeč
- membránové proteiny MeSH
- pirinixic acid MeSH Prohlížeč
- PPAR alfa MeSH
- PPAR gama MeSH
- proteinové prekurzory MeSH
- proteiny intermediálních filament MeSH
- pyrimidiny MeSH
- testosteron MeSH
- thiazolidindiony 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
Citace poskytuje Crossref.org
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