-
Something wrong with this record ?
Filaggrin deficiency leads to impaired lipid profile and altered acidification pathways in a 3D skin construct
K. Vávrová, D. Henkes, K. Strüver, M. Sochorová, B. Skolová, MY. Witting, W. Friess, S. Schreml, RJ. Meier, M. Schäfer-Korting, JW. Fluhr, S. Küchler,
Language English Country United States
Document type Journal Article, Research Support, Non-U.S. Gov't
NLK
Free Medical Journals
from 1938 to 1 year ago
Freely Accessible Science Journals
from 1938 to 1 year ago
ProQuest Central
from 2000-01-01 to 2015-12-31
Open Access Digital Library
from 1938-01-01
Health & Medicine (ProQuest)
from 2000-01-01 to 2015-12-31
PubMed
24061166
DOI
10.1038/jid.2013.402
Knihovny.cz E-resources
- MeSH
- Dermatitis, Atopic metabolism pathology MeSH
- Group II Phospholipases A2 metabolism MeSH
- Gene Knockdown Techniques MeSH
- Hydrogen-Ion Concentration MeSH
- Skin cytology metabolism MeSH
- Pyrrolidonecarboxylic Acid metabolism MeSH
- Urocanic Acid metabolism MeSH
- Fatty Acids, Nonesterified metabolism MeSH
- Acids metabolism MeSH
- Humans MeSH
- Lipid Metabolism physiology MeSH
- Sodium-Hydrogen Exchangers metabolism MeSH
- Permeability MeSH
- Intermediate Filament Proteins deficiency genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
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 A2 (sPLA2) IIA, which converts phospholipids to fatty acids, was significantly more activated in FLG- than in FLG+. Although NHE-1 and sPLA2 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 sPLA2/NHE-1 acidification pathways of the skin and the impact of FLG insufficiency on skin lipid composition and organization in reconstructed skin are described.
Department of Dermatology Charité University Clinic Berlin Germany
Department of Dermatology University Medical Center Regensburg Regensburg Germany
Department of Pharmacy Ludwig Maximilians University Munich Munich Germany
Faculty of Pharmacy Charles University Prague Hradec Kralove Czech Republic
Institute for Pharmacy Pharmacology and Toxicology Freie Universität Berlin Berlin Germany
Institute of Analytical Chemistry Chemo and Biosensors University of Regensburg Regensburg Germany
References provided by Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc14063943
- 003
- CZ-PrNML
- 005
- 20140708094647.0
- 007
- ta
- 008
- 140704s2014 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1038/jid.2013.402 $2 doi
- 035 __
- $a (PubMed)24061166
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Vávrová, Kateřina $u Faculty of Pharmacy, Charles University in Prague, Hradec Kralove, Czech Republic.
- 245 10
- $a Filaggrin deficiency leads to impaired lipid profile and altered acidification pathways in a 3D skin construct / $c K. Vávrová, D. Henkes, K. Strüver, M. Sochorová, B. Skolová, MY. Witting, W. Friess, S. Schreml, RJ. Meier, M. Schäfer-Korting, JW. Fluhr, S. Küchler,
- 520 9_
- $a 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 A2 (sPLA2) IIA, which converts phospholipids to fatty acids, was significantly more activated in FLG- than in FLG+. Although NHE-1 and sPLA2 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 sPLA2/NHE-1 acidification pathways of the skin and the impact of FLG insufficiency on skin lipid composition and organization in reconstructed skin are described.
- 650 _2
- $a kyseliny $x metabolismus $7 D000143
- 650 _2
- $a atopická dermatitida $x metabolismus $x patologie $7 D003876
- 650 _2
- $a kyseliny mastné neesterifikované $x metabolismus $7 D005230
- 650 _2
- $a genový knockdown $7 D055785
- 650 _2
- $a fosfolipasy A2, skupina II $x metabolismus $7 D054501
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a koncentrace vodíkových iontů $7 D006863
- 650 _2
- $a proteiny intermediálních filament $x nedostatek $x genetika $7 D007381
- 650 _2
- $a metabolismus lipidů $x fyziologie $7 D050356
- 650 _2
- $a permeabilita $7 D010539
- 650 _2
- $a kyselina pyrrolidonkarboxylová $x metabolismus $7 D011761
- 650 _2
- $a kůže $x cytologie $x metabolismus $7 D012867
- 650 _2
- $a Na(+)-H(+) antiport $x metabolismus $7 D017923
- 650 _2
- $a kyselina urokanová $x metabolismus $7 D014560
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Henkes, Dominika $u Institute for Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Berlin, Germany.
- 700 1_
- $a Strüver, Kay $u Department of Pharmacy, Ludwig-Maximilians University Munich, Munich, Germany.
- 700 1_
- $a Sochorová, Michaela $u Faculty of Pharmacy, Charles University in Prague, Hradec Kralove, Czech Republic.
- 700 1_
- $a Skolová, Barbora $u Faculty of Pharmacy, Charles University in Prague, Hradec Kralove, Czech Republic.
- 700 1_
- $a Witting, Madeleine Y $u Department of Pharmacy, Ludwig-Maximilians University Munich, Munich, Germany.
- 700 1_
- $a Friess, Wolfgang $u Department of Pharmacy, Ludwig-Maximilians University Munich, Munich, Germany.
- 700 1_
- $a Schreml, Stephan $u Department of Dermatology, University Medical Center Regensburg, Regensburg, Germany.
- 700 1_
- $a Meier, Robert J $u Institute of Analytical Chemistry, Chemo- and Biosensors, University of Regensburg, Regensburg, Germany.
- 700 1_
- $a Schäfer-Korting, Monika $u Institute for Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Berlin, Germany.
- 700 1_
- $a Fluhr, Joachim W $u Department of Dermatology, Charité University Clinic, Berlin, Germany.
- 700 1_
- $a Küchler, Sarah $u Institute for Pharmacy, Pharmacology and Toxicology, Freie Universität Berlin, Berlin, Germany.
- 773 0_
- $w MED00002756 $t The Journal of investigative dermatology $x 1523-1747 $g Roč. 134, č. 3 (2014), s. 746-53
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/24061166 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20140704 $b ABA008
- 991 __
- $a 20140708094936 $b ABA008
- 999 __
- $a ok $b bmc $g 1031427 $s 862675
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2014 $b 134 $c 3 $d 746-53 $i 1523-1747 $m Journal of investigative dermatology $n J Invest Dermatol $x MED00002756
- LZP __
- $a Pubmed-20140704
