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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Vydané v:	Journal of investigative dermatology Ročník 138; číslo 6; s. 1311
Hlavní autori:	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:	English
Vydavateľské údaje:	United States 01.06.2018
Predmet:	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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Abstract	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.
AbstractList	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. 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.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.
Author	Mollanazar, Nicholas K Yosipovitch, Gil Valdes-Rodriguez, Rodrigo Sanders, Kristen M Tey, Hong Liang Albornoz, Christian Nattkemper, Leigh A Lee, Helen
Author_xml	– sequence: 1 givenname: Leigh A surname: Nattkemper fullname: Nattkemper, Leigh A organization: Department of Dermatology, Miami Itch Center, University of Miami Miller School of Medicine, Miami, Florida, USA – sequence: 2 givenname: Hong Liang surname: Tey fullname: Tey, Hong Liang organization: Department of Dermatology, National Skin Center, Singapore, Singapore – sequence: 3 givenname: Rodrigo surname: Valdes-Rodriguez fullname: Valdes-Rodriguez, Rodrigo organization: Department of Dermatology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA – sequence: 4 givenname: Helen surname: Lee fullname: Lee, Helen organization: Department of Dermatology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA – sequence: 5 givenname: Nicholas K surname: Mollanazar fullname: Mollanazar, Nicholas K organization: Department of Dermatology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA – sequence: 6 givenname: Christian surname: Albornoz fullname: Albornoz, Christian organization: Department of Dermatology, Temple University Lewis Katz School of Medicine, Philadelphia, Pennsylvania, USA – sequence: 7 givenname: Kristen M surname: Sanders fullname: Sanders, Kristen M organization: Department of Dermatology, Miami Itch Center, University of Miami Miller School of Medicine, Miami, Florida, USA – sequence: 8 givenname: Gil surname: Yosipovitch fullname: Yosipovitch, Gil email: gyosipovitch@med.miami.edu organization: Department of Dermatology, Miami Itch Center, University of Miami Miller School of Medicine, Miami, Florida, USA. Electronic address: gyosipovitch@med.miami.edu
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Snippet	To identify itch-related mediators and receptors that are differentially expressed in pruritic skin, we used RNA sequencing to analyze the complete...
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SubjectTerms	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
Title	The Genetics of Chronic Itch: Gene Expression in the Skin of Patients with Atopic Dermatitis and Psoriasis with Severe Itch
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Volume	138
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