• Je něco špatně v tomto záznamu ?

Stimulation of PPARα normalizes the skin lipid ratio and improves the skin barrier of normal and filaggrin deficient reconstructed skin

L. Wallmeyer, D. Lehnen, N. Eger, M. Sochorová, L. Opálka, A. Kováčik, K. Vávrová, S. Hedtrich,

. 2015 ; 80 (2) : 102-10. [pub] 20151009

Jazyk angličtina Země Nizozemsko

Typ dokumentu časopisecké články, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc16028088

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.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc16028088
003      
CZ-PrNML
005      
20161025094521.0
007      
ta
008      
161005s2015 ne f 000 0|eng||
009      
AR
024    7_
$a 10.1016/j.jdermsci.2015.09.012 $2 doi
024    7_
$a 10.1016/j.jdermsci.2015.09.012 $2 doi
035    __
$a (PubMed)26472199
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a ne
100    1_
$a Wallmeyer, Leonie $u Institute for Pharmaceutical Sciences, Pharmacology and Toxicology, Freie Universität Berlin, Germany.
245    10
$a Stimulation of PPARα normalizes the skin lipid ratio and improves the skin barrier of normal and filaggrin deficient reconstructed skin / $c L. Wallmeyer, D. Lehnen, N. Eger, M. Sochorová, L. Opálka, A. Kováčik, K. Vávrová, S. Hedtrich,
520    9_
$a 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.
650    _2
$a kultivované buňky $7 D002478
650    _2
$a kyseliny dokosahexaenové $x farmakologie $7 D004281
650    _2
$a kyseliny mastné neesterifikované $x metabolismus $7 D005230
650    _2
$a fibroblasty $x účinky léků $x metabolismus $7 D005347
650    _2
$a genotyp $7 D005838
650    _2
$a lidé $7 D006801
650    _2
$a proteiny intermediálních filament $x nedostatek $x genetika $7 D007381
650    _2
$a metabolismus lipidů $x účinky léků $7 D050356
650    _2
$a membránové proteiny $x genetika $x metabolismus $7 D008565
650    _2
$a PPAR alfa $x agonisté $x metabolismus $7 D047493
650    _2
$a PPAR gama $x agonisté $x metabolismus $7 D047495
650    _2
$a permeabilita $7 D010539
650    _2
$a fenotyp $7 D010641
650    _2
$a proteinové prekurzory $x genetika $x metabolismus $7 D011498
650    _2
$a pyrimidiny $x farmakologie $7 D011743
650    _2
$a RNA interference $7 D034622
650    _2
$a signální transdukce $x účinky léků $7 D015398
650    _2
$a kůže $x účinky léků $x metabolismus $7 D012867
650    _2
$a kožní absorpce $x účinky léků $7 D012869
650    _2
$a testosteron $x metabolismus $7 D013739
650    _2
$a thiazolidindiony $x farmakologie $7 D045162
650    _2
$a časové faktory $7 D013997
650    _2
$a transfekce $7 D014162
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Lehnen, Dominika $u Institute for Pharmaceutical Sciences, Pharmacology and Toxicology, Freie Universität Berlin, Germany.
700    1_
$a Eger, Natascha $u Institute for Pharmaceutical Sciences, Pharmacology and Toxicology, Freie Universität Berlin, Germany.
700    1_
$a Sochorová, Michaela $u Charles University Prague, Faculty of Pharmacy, Hradec Kralove, Czech Republic.
700    1_
$a Opálka, Lukáš $u Charles University Prague, Faculty of Pharmacy, Hradec Kralove, Czech Republic.
700    1_
$a Kováčik, Andrej $u Charles University Prague, Faculty of Pharmacy, Hradec Kralove, Czech Republic.
700    1_
$a Vávrová, Kateřina $u Charles University Prague, Faculty of Pharmacy, Hradec Kralove, Czech Republic.
700    1_
$a Hedtrich, Sarah $u Institute for Pharmaceutical Sciences, Pharmacology and Toxicology, Freie Universität Berlin, Germany. Electronic address: sarah.hedtrich@fu-berlin.de.
773    0_
$w MED00006643 $t Journal of dermatological science $x 1873-569X $g Roč. 80, č. 2 (2015), s. 102-10
856    41
$u https://pubmed.ncbi.nlm.nih.gov/26472199 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20161005 $b ABA008
991    __
$a 20161025094934 $b ABA008
999    __
$a ok $b bmc $g 1166402 $s 952718
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2015 $b 80 $c 2 $d 102-10 $e 20151009 $i 1873-569X $m Journal of dermatological science $n J Dermatol Sci $x MED00006643
LZP    __
$a Pubmed-20161005

Najít záznam

Citační ukazatele

Možnosti archivace