Superficial dsg2 expression limits epidermal blister formation mediated by pemphigus foliaceus antibodies and exfoliative toxins.
Superficial dsg2 expression limits epidermal blister formation mediated by pemphigus foliaceus antibodies and exfoliative toxins.
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DOI：
10.1155/2010/410278
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发表时间：
2010
影响因子：
1.5
通讯作者：
Mahoney MG
中科院分区：
文献类型：
--
作者：
Brennan D;Hu Y;Medhat W;Dowling A;Mahoney MG
桥粒介导的细胞-细胞黏附对于维持正常的表皮结构和功能至关重要，几种严重和潜在致命的皮肤病都证明了这一点，这些疾病包括桥粒蛋白的损伤。叶状天疱疮(Pf)和金黄色葡萄球菌烫伤皮肤综合征(SSSS)是由于桥粒钙粘蛋白1(DSG1)功能丧失而引起的角膜下水泡性疾病。为了进一步研究这些疾病的发病机制，并评估Dsg2的粘附性，我们采用了最近建立的在浅层表皮表达Dsg2的转基因(TG)小鼠模型。新生的TG和野生型(WT)小鼠分别注射纯化的ETA或PF Ig。我们发现，Dsg2的异位表达减少了ETA和PF Ig对水泡形成的程度。作为对PfIg的反应，我们在WT小鼠中观察到DSG1-α、DSG1-β以及较小程度的DSG1-γ的急剧丢失或重组。Inv-Dsg2转基因小鼠显示DSG1在细胞-细胞边界的滞留增强。总之，我们的数据支持Dsg2在细胞黏附中的作用，并表明异位表面表达Dsg2可以增加DSG1的膜保存性，并限制由PF抗体和脱落毒素介导的表皮水泡的形成。
Cell-cell adhesion mediated by desmosomes is crucial for maintaining proper epidermal structure and function, as evidenced by several severe and potentially fatal skin disorders involving impairment of desmosomal proteins. Pemphigus foliaceus (PF) and staphylococcal scalded skin syndrome (SSSS) are subcorneal blistering diseases resulting from loss of function of the desmosomal cadherin, desmoglein 1 (Dsg1). To further study the pathomechanism of these diseases and to assess the adhesive properties of Dsg2, we employed a recently established transgenic (Tg) mouse model expressing Dsg2 in the superficial epidermis. Neonatal Tg and wild type (WT) mice were injected with purified ETA or PF Ig. We showed that ectopic expression of Dsg2 reduced the extent of blister formation in response to both ETA and PF Ig. In response to PF Ig, we observed either a dramatic loss or a reorganization of Dsg1-α, Dsg1-β, and, to a lesser extent, Dsg1-γ, in WT mice. The Inv-Dsg2 Tg mice showed enhanced retention of Dsg1 at the cell-cell border. Collectively, our data support the role for Dsg2 in cell adhesion and suggest that ectopic superficial expression of Dsg2 can increase membrane preservation of Dsg1 and limit epidermal blister formation mediated by PF antibodies and exfoliative toxins.