Filaggrin Deficiency Leads to Impaired Lipid Profile and Altered Acidification Pathways in a 3D Skin Construct

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F14%3A10281664" target="_blank" >RIV/00216208:11160/14:10281664 - isvavai.cz</a>

Výsledek na webu

<a href="http://www.nature.com/jid/journal/v134/n3/full/jid2013402a.html" target="_blank" >http://www.nature.com/jid/journal/v134/n3/full/jid2013402a.html</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/jid.2013.402" target="_blank" >10.1038/jid.2013.402</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Filaggrin Deficiency Leads to Impaired Lipid Profile and Altered Acidification Pathways in a 3D Skin Construct

Popis výsledku v původním jazyce

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 d

Název v anglickém jazyce

Filaggrin Deficiency Leads to Impaired Lipid Profile and Altered Acidification Pathways in a 3D Skin Construct

Popis výsledku anglicky

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 d

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FR - Farmakologie a lékárnická chemie

OECD FORD obor

—

Projekt

<a href="/cs/project/GAP207%2F11%2F0365" target="_blank" >GAP207/11/0365: Syntéza a studium strukturních závislostí ceramidů v kůži a látek s nimi interagujících</a><br>

Návaznosti

S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2014

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Investigative Dermatology

ISSN

0022-202X

e-ISSN

—

Svazek periodika

134

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

8

Strana od-do

746-753

Kód UT WoS článku

000331669800024

EID výsledku v databázi Scopus

—