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



Blunder, Stefan, Koks, Sulev ORCID: 0000-0001-6087-6643, Koks, Gea, Reimann, Ene, Hackl, Hubert, Gruber, Robert, Moosbrugger-Martinz, Verena, Schmuth, Matthias and Dubrac, Sandrine
(2018) Enhanced Expression of Genes Related to Xenobiotic Metabolism in the Skin of Patients with Atopic Dermatitis but Not with Ichthyosis Vulgaris. JOURNAL OF INVESTIGATIVE DERMATOLOGY, 138 (1). pp. 98-108.

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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.

Item Type: Article
Uncontrolled Keywords: Skin, Humans, Ichthyosis Vulgaris, Dermatitis, Atopic, Intermediate Filament Proteins, Xenobiotics, Case-Control Studies, Cohort Studies, Gene Expression Profiling, Sequence Analysis, RNA, Down-Regulation, Up-Regulation, Adult, Aged, Middle Aged, Female, Male, Metabolic Networks and Pathways, Young Adult, Healthy Volunteers, Loss of Function Mutation, Filaggrin Proteins
Depositing User: Symplectic Admin
Date Deposited: 04 Jan 2019 15:21
Last Modified: 19 Jan 2023 01:08
DOI: 10.1016/j.jid.2017.08.036
Open Access URL: https://www.sciencedirect.com/science/article/pii/...
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URI: https://livrepository.liverpool.ac.uk/id/eprint/3030785