The Genetics of Chronic Itch: Gene Expression in the Skin of Patients with Atopic Dermatitis and Psoriasis with Severe Itch
The Genetics of Chronic Itch: Gene Expression in the Skin of Patients with Atopic Dermatitis and Psoriasis with Severe Itch
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DOI：
10.1016/j.jid.2017.12.029
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发表时间：
2018-06-01
影响因子：
6.5
通讯作者：
Yosipovitch, Gil
中科院分区：
文献类型：
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作者：
Nattkemper, Leigh A.;Tey, Hong Liang;Yosipovitch, Gil
为了鉴定瘙痒相关介质和受体在过敏性皮肤中的差异表达，我们使用RNA测序分析了来自25名特应性皮炎患者和25名银屑病患者的成对瘙痒、病变和非瘙痒、非病变皮肤活检组织以及来自30名健康对照的位点匹配活检组织的皮肤中的完整转录组。这项分析确定了与健康皮肤相比，特应性瘙痒和银屑病皮肤之间共有的18，000个差异表达基因。其中，近2,000个基因在特应性和银屑病受试者的瘙痒和非瘙痒皮肤之间差异表达。几个基因，如磷脂酶A2 IVD，P物质，电压门控钠通道1.7，和瞬时受体电位（TRP）香草酸1，在瘙痒的皮肤中的过度表达与过敏性皮炎和银屑病的瘙痒强度等级呈正相关。细胞因子如IL-17 A、IL-23 A和IL-31在瘙痒特应性皮肤和银屑病皮肤中的基因转录水平升高。然而，TRP香草素2、TRP锚蛋白1、蛋白酶激活受体2、蛋白酶激活受体4和IL-10的基因表达仅在银屑病特应性皮肤中增加，而TRP melastatin 8、TRP香草素3、磷脂酶C和IL-36 a/g的基因表达仅在银屑病皮肤中升高。这种"瘙痒脚本"分析将导致对慢性瘙痒的分子机制的更多理解，并提供瘙痒治疗的靶点，而不管疾病状态如何。
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-36a/g 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.