The Genetics of Chronic Itch: Gene Expression in the Skin of Patients with Atopic Dermatitis and Psoriasis with Severe Itch

To identify itch-related mediators and receptors that are differentially expressed in pruritic skin, we used RNA sequencing to analyze the complete transcriptome in skin from paired itchy, lesional and nonitchy, nonlesional skin biopsies from 25 patients with atopic dermatitis and 25 patients with p...

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Vydáno v:Journal of investigative dermatology Ročník 138; číslo 6; s. 1311
Hlavní autoři: Nattkemper, Leigh A, Tey, Hong Liang, Valdes-Rodriguez, Rodrigo, Lee, Helen, Mollanazar, Nicholas K, Albornoz, Christian, Sanders, Kristen M, Yosipovitch, Gil
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States 01.06.2018
Témata:
Adult
Biopsy
Chronic Disease
Dermatitis, Atopic - complications
Dermatitis, Atopic - genetics
Dermatitis, Atopic - immunology
Dermatitis, Atopic - pathology
Female
Gene Expression Profiling
Healthy Volunteers
Humans
Male
Middle Aged
Pruritus - genetics
Pruritus - immunology
Pruritus - pathology
Psoriasis - complications
Psoriasis - genetics
Psoriasis - immunology
Psoriasis - pathology
Sequence Analysis, RNA
Skin - pathology
Transcriptome - immunology
ISSN:1523-1747, 1523-1747
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Popis
Shrnutí:To identify itch-related mediators and receptors that are differentially expressed in pruritic skin, we used RNA sequencing to analyze the complete transcriptome in skin from paired itchy, lesional and nonitchy, nonlesional skin biopsies from 25 patients with atopic dermatitis and 25 patients with psoriasis and site-matched biopsies from 30 healthy controls. This analysis identified 18,000 differentially expressed genes common between itchy atopic and psoriatic skin compared with healthy skin. Of those, almost 2,000 genes were differentially expressed between itchy and nonitchy skin in atopic and psoriatic subjects. Overexpression of several genes, such as phospholipase A2 IVD, substance P, voltage-gated sodium channel 1.7, and transient receptor potential (TRP) vanilloid 1, in itchy skin was positively correlated with itch intensity ratings in both atopic dermatitis and psoriasis. Cytokines such as IL-17A, IL-23A, and IL-31 had elevated gene transcript levels in both itchy atopic and psoriatic skin. However, expression of genes for TRP vanilloid 2, TRP ankyrin 1, protease-activated receptor 2, protease-activated receptor 4, and IL-10 was found to be increased only in pruritic atopic skin, whereas expression of genes for TRP melastatin 8, TRP vanilloid 3, phospholipase C, and IL-36α/γ was elevated only in pruritic psoriatic skin. This "itchscriptome" analysis will lead to an increased understanding of the molecular mechanisms of chronic pruritus and provide targets for itch treatment irrespective of disease state.
Bibliografie:ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:1523-1747
1523-1747
DOI:10.1016/j.jid.2017.12.029