TY - JOUR
T1 - Skin of atopic dermatitis patients shows disturbed β-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition
AU - Boer, Daphne E C
AU - van Smeden, Jeroen
AU - Al-Khakany, Hanin
AU - Melnik, Elizaveta
AU - van Dijk, Rianne
AU - Absalah, Samira
AU - Vreeken, Rob J
AU - Haenen, Caroline C P
AU - Lavrijsen, Adriana P M
AU - Overkleeft, Herman S
AU - Aerts, Johannes M F G
AU - Bouwstra, Joke A
N1 - Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.
PY - 2020/6
Y1 - 2020/6
N2 - Patients with Atopic Dermatitis (AD) suffer from inflamed skin and skin barrier defects. Proper formation of the outermost part of the skin, the stratum corneum (SC), is crucial for the skin barrier function. In this study we analyzed the localization and activity of lipid enzymes β-glucocerebrosidase (GBA) and acid sphingomyelinase (ASM) in the skin of AD patients and controls. Localization of both the expression and activity of GBA and ASM in the epidermis of AD patients was altered, particularly at lesional skin sites. These changes aligned with the altered SC lipid composition. More specifically, abnormal localization of GBA and ASM related to an increase in specific ceramide subclasses [AS] and [NS]. Moreover we related the localization of the enzymes to the amounts of SC ceramide subclasses and free fatty acids (FFAs). We report a correlation between altered localization of active GBA and ASM and a disturbed SC lipid composition. Localization of antimicrobial peptide beta-defensin-3 (HBD-3) and AD biomarker Thymus and Activation Regulated Chemokine (TARC) also appeared to be diverging in AD skin compared to control. This research highlights the relation between correct localization of expressed and active lipid enzymes and a normal SC lipid composition for a proper skin barrier.
AB - Patients with Atopic Dermatitis (AD) suffer from inflamed skin and skin barrier defects. Proper formation of the outermost part of the skin, the stratum corneum (SC), is crucial for the skin barrier function. In this study we analyzed the localization and activity of lipid enzymes β-glucocerebrosidase (GBA) and acid sphingomyelinase (ASM) in the skin of AD patients and controls. Localization of both the expression and activity of GBA and ASM in the epidermis of AD patients was altered, particularly at lesional skin sites. These changes aligned with the altered SC lipid composition. More specifically, abnormal localization of GBA and ASM related to an increase in specific ceramide subclasses [AS] and [NS]. Moreover we related the localization of the enzymes to the amounts of SC ceramide subclasses and free fatty acids (FFAs). We report a correlation between altered localization of active GBA and ASM and a disturbed SC lipid composition. Localization of antimicrobial peptide beta-defensin-3 (HBD-3) and AD biomarker Thymus and Activation Regulated Chemokine (TARC) also appeared to be diverging in AD skin compared to control. This research highlights the relation between correct localization of expressed and active lipid enzymes and a normal SC lipid composition for a proper skin barrier.
KW - Adolescent
KW - Adult
KW - Biopsy
KW - Case-Control Studies
KW - Ceramides/analysis
KW - Chemokine CCL17/metabolism
KW - Dermatitis, Atopic/immunology
KW - Epidermis/chemistry
KW - Fatty Acids, Nonesterified/analysis
KW - Female
KW - Glucosylceramidase/metabolism
KW - Healthy Volunteers
KW - Humans
KW - Lipid Metabolism/immunology
KW - Male
KW - Sphingomyelin Phosphodiesterase/metabolism
KW - Water Loss, Insensible/immunology
KW - Young Adult
KW - beta-Defensins/metabolism
UR - https://www.scopus.com/pages/publications/85080034061
UR - https://www.scopus.com/inward/citedby.url?scp=85080034061&partnerID=8YFLogxK
U2 - 10.1016/j.bbalip.2020.158673
DO - 10.1016/j.bbalip.2020.158673
M3 - Article
C2 - 32092464
SN - 1388-1981
VL - 1865
SP - 158673
JO - Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
JF - Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
IS - 6
M1 - 158673
ER -