Downregulation of Caveolae-Associated Proteins in Psoriasis: A Case Series Study

Deborah A. Lin , Beatriz Abdo Abujamra , Stephanie Revah , Leigh Nattkemper , Brian Morrison , Paolo Romanelli , Ivan Jozic
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Abstract

We have previously identified that a structural membrane protein Caveolin-1 (Cav1) is involved in the regulation of aberrant keratinocyte proliferation and differentiation. The aim of this study was to elucidate the role of Cav1, Caveolin-2 (Cav2), and Cavin-1 in the pathogenesis of psoriasis vulgaris and between psoriasis subtypes. We utilized human biopsies from validated cases of psoriasis vulgaris (n = 21) at the University of Miami Hospital and compared the expression of Cav1, Cav2, and Cavin-1 by immunohistochemistry staining with that in normal healthy age-/sex-/location-matched skin (n = 15) and chronic spongiotic dermatitis skin samples (as control inflammatory skin condition) and quantified using QuPath. Distinct subtypes of psoriasis included guttate, inverse, nail, plaque, palmoplantar, and pustular. All biopsy samples exhibited a trend toward downregulation of Cav1, with nail, plaque, and palmoplantar psoriasis exhibiting the most pronounced effects. Only nail and pustular psoriasis samples exhibited significant downregulation of Cav2 and Cavin-1, suggesting Cav1 to be the main caveolar contributor to the pathogenesis of psoriasis. Together, these data support caveolae as pathophysiological targets in nail and pustular psoriasis, whereas Cav1 seems to be a general biomarker of multiple subtypes of psoriasis.

牛皮癣中 Caveolae 相关蛋白的下调:一项病例系列研究
我们以前曾发现,结构膜蛋白 Caveolin-1 (Cav1) 参与调节角质形成细胞的异常增殖和分化。本研究旨在阐明 Cav1、Caveolin-2(Cav2)和 Cavin-1 在寻常型银屑病的发病机制中以及不同亚型银屑病中的作用。我们利用迈阿密大学医院确诊的寻常型银屑病病例(n = 21)的人体活组织切片,通过免疫组化染色将 Cav1、Cav2 和 Cavin-1 的表达与年龄/性别/地点匹配的正常健康皮肤(n = 15)和慢性海绵状皮炎皮肤样本(作为炎症性皮肤的对照)进行比较,并使用 QuPath 进行量化。银屑病的不同亚型包括凹陷型、逆转型、指甲型、斑块型、掌跖型和脓疱型。所有活检样本都显示出 Cav1 的下调趋势,其中指甲、斑块和掌跖银屑病的影响最为明显。只有指甲和脓疱型银屑病样本表现出 Cav2 和 Cavin-1 的显著下调,这表明 Cav1 是导致银屑病发病的主要洞穴因子。总之,这些数据支持洞穴是指甲型银屑病和脓疱型银屑病的病理生理靶点,而Cav1似乎是多种亚型银屑病的通用生物标志物。
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