Wan Hong, Dopping-Hepenstal Patricia J C, Gratian Matthew J, Stone Michael G, McGrath John A, Eady Robin A J
Department of Cell and Molecular Pathology, St John's Institute of Dermatology, London, UK.
Exp Dermatol. 2003 Aug;12(4):378-88. doi: 10.1034/j.1600-0625.2002.120404.x.
Hereditary skin disorders resulting from desmosome gene pathology may preferentially involve the palms and soles. Why this is so is not clear. Moreover, even in normal control skin it is unknown whether there are differences in desmosome number, size or structural organization in palmoplantar sites compared with skin from other body regions. Therefore, we sought evidence for such differences by examining desmosome expression in relation to epidermal differentiation in both epidermis and cultured keratinocytes from normal human palm and breast skin samples. Confocal microscopy of skin biopsy material showed relative differences in the expression profiles of several desmosomal proteins (desmogleins, desmocollins, desmoplakin, plakoglobin and plakophilin 1) between the two sites. Western blotting revealed a higher expression level of all five proteins in palm compared with breastcultured keratinocytes. Staining for the differentiation-associated component, involucrin, suggested an earlier onset of synthesis of this protein in palm epidermis, and a suspension-induced differentiation assay showed that involucrin synthesis began earlier in palm keratinocytes than in breast cells. At 4-8 h, the number of involucrin-positive cells in palm keratinocytes was almost twice that in breast. Morphometric analysis showed that, overall, desmosomes were larger but of similar population density in the palm compared with breast skin. These findings demonstrate differences in desmosome structure and protein expression between the two sites, possibly reflecting the needs of palms and soles to withstand constant mechanical stress. They may also help to explain the preferential involvement of this region in certain hereditary disorders (palmoplantar keratodermas), associated with mutations in desmoplakin or desmoglein 1.
由桥粒基因病变引起的遗传性皮肤病可能优先累及手掌和足底。原因尚不清楚。此外,即使在正常对照皮肤中,与身体其他部位的皮肤相比,掌跖部位的桥粒数量、大小或结构组织是否存在差异也不清楚。因此,我们通过检测正常人类手掌和乳房皮肤样本的表皮及培养角质形成细胞中桥粒表达与表皮分化的关系,来寻找这种差异的证据。皮肤活检材料的共聚焦显微镜检查显示,两个部位之间几种桥粒蛋白(桥粒芯糖蛋白、桥粒芯胶蛋白、桥粒斑蛋白、桥粒珠蛋白和桥粒斑菲素蛋白1)的表达谱存在相对差异。蛋白质印迹法显示,与乳房培养的角质形成细胞相比,手掌中所有这五种蛋白的表达水平更高。对分化相关成分内披蛋白的染色表明,该蛋白在手掌表皮中的合成起始较早,悬浮诱导分化试验表明,手掌角质形成细胞中内披蛋白的合成比乳房细胞开始得更早。在4 - 8小时时,手掌角质形成细胞中内披蛋白阳性细胞的数量几乎是乳房中的两倍。形态计量分析表明,总体而言,与乳房皮肤相比,手掌中的桥粒更大,但群体密度相似。这些发现证明了两个部位之间桥粒结构和蛋白表达的差异,这可能反映了手掌和足底承受持续机械应力的需求。它们也可能有助于解释该区域在某些与桥粒斑蛋白或桥粒芯糖蛋白1突变相关的遗传性疾病(掌跖角化病)中的优先受累情况。