Enhanced Expression of Genes Related to Xenobiotic Metabolism in the Skin of Patients with Atopic Dermatitis but Not with Ichthyosis Vulgaris.

Abstract

Previous transcriptome analyses underscored the importance of immunological and skin barrier abnormalities in atopic dermatitis (AD). We sought to identify pathogenic pathways involved in AD by comparing the transcriptomes of AD patients stratified for filaggrin (FLG)-null mutations to those of both healthy donors and patients with ichthyosis vulgaris. We applied RNA sequencing to analyze the whole transcriptome of nonlesional skin. We found that 607 genes (476 up-regulated and 131 down-regulated by >2-fold) and 193 genes (172 up-regulated and 21 down-regulated by >2-fold) were differentially expressed when all AD or ichthyosis vulgaris patients were compared with healthy donors, respectively. Expression of genes involved in RNA/protein turnover and adenosine triphosphate synthesis, as well as genes involved in cell death, response to oxidative stress, DNA damage/repair, and autophagy, were significantly enriched in AD skin and, to a lesser extent, in ichthyosis vulgaris skin. FLG-null mutations appear to hardly interfere with current observations. Genes related to xenobiotic metabolism were up-regulated in AD skin only, as were genes related to arachidonic, linoleic, and α-linolenic acid metabolism. Thus, this work newly links AD pathogenesis to aberrant expression of genes related to xenobiotic metabolism.

• Authors: Stefan Blunder, Sulev Kõks, Gea Kõks, Ene Reimann, Hubert Hackl, Robert Gruber, Verena Moosbrugger-Martinz, Matthias Schmuth, Sandrine Dubrac
• Journal: The Journal of investigative dermatology (J Invest Dermatol) Vol. 138 Issue 1 Pg. 98-108 (01 2018) ISSN: 1523-1747 [Electronic] United States
• PMID: 28899689 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• FLG protein, human
• Filaggrin Proteins
• Intermediate Filament Proteins
• Xenobiotics

Topics

• Adult
• Aged
• Case-Control Studies
• Cohort Studies
• Dermatitis, Atopic (etiology, genetics, pathology)
• Down-Regulation
• Female
• Filaggrin Proteins
• Gene Expression Profiling
• Healthy Volunteers
• Humans
• Ichthyosis Vulgaris (etiology, genetics, pathology)
• Intermediate Filament Proteins (genetics)
• Loss of Function Mutation
• Male
• Metabolic Networks and Pathways (genetics)
• Middle Aged
• Sequence Analysis, RNA
• Skin (metabolism, pathology)
• Up-Regulation
• Xenobiotics (metabolism)
• Young Adult