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Biochim Biophys Acta Mol Cell Biol Lipids. 2020 Jun;1865(6):158673. doi: 10.1016/j.bbalip.2020.158673. Epub 2020 Feb 21.

Skin of atopic dermatitis patients shows disturbed β-glucocerebrosidase and acid sphingomyelinase activity that relates to changes in stratum corneum lipid composition.

Author information

1
Leiden Institute of Chemistry, Leiden University, Leiden, the Netherlands.
2
Leiden Academic Centre for Drug Research, Leiden, the Netherlands; Centre for Human Drug Research, Leiden, the Netherlands.
3
Leiden Academic Centre for Drug Research, Leiden, the Netherlands.
4
Centre for Human Drug Research, Leiden, the Netherlands.
5
Leiden Academic Centre for Drug Research, Leiden, the Netherlands; M4I Institute, Maastricht University, Maastricht, the Netherlands.
6
Department of Dermatology, Leiden University Medical Center, Leiden, the Netherlands.
7
Leiden Academic Centre for Drug Research, Leiden, the Netherlands. Electronic address: bouwstra@lacdr.leidenuniv.nl.

Abstract

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.

KEYWORDS:

Acid sphingomyelinase; Atopic dermatitis; Fluorescence microscopy; Glucocerebrosidase; Mass spectrometry; Stratum corneum

PMID:
32092464
DOI:
10.1016/j.bbalip.2020.158673
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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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