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

Daphne E. C. Boer, Jeroen van Smeden, Hanin Al-Khakany, Elizaveta Melnik, Rianne van Dijk, Samira Absalah, Rob J. Vreeken, Caroline C. P. Haenen, Adriana P. M. Lavrijsen, Herman S. Overkleeft, Johannes M. F. G. Aerts, Joke A. Bouwstra*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

14 Citations (Web of Science)

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 beta-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.

Original languageEnglish
Article number158673
Number of pages10
JournalBiochimica et Biophysica Acta-Molecular and Cell Biology of Lipids
Volume1865
Issue number6
DOIs
Publication statusPublished - Jun 2020

Keywords

  • Atopic dermatitis
  • Stratum corneum
  • Glucocerebrosidase
  • Acid sphingomyelinase
  • Mass spectrometry
  • Fluorescence microscopy
  • ACTIVATION-REGULATED CHEMOKINE
  • IN-SITU VISUALIZATION
  • BARRIER FUNCTION
  • SERUM THYMUS
  • FILAGGRIN
  • ORGANIZATION
  • MAINTENANCE
  • PRECURSORS
  • BIOMARKERS
  • CHILDREN

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