Raiko Laura, Leinonen Pekka, Hägg Päivi M, Peltonen Juha, Oikarinen Aarne, Peltonen Sirkku
Department of Dermatology, University of Turku and Turku University Central Hospital, Turku, Finland;
Department of Anatomy and Cell Biology and ; Department of Dermatology, University of Oulu, Oulu, Finland;
Dermatol Reports. 2009 Nov 13;1(1):e1. doi: 10.4081/dr.2009.e1. eCollection 2009 Nov 16.
Hailey-Hailey disease (HHD) and Darier's disease (DD) are caused by mutations in Ca(2+)-ATPases with the end result of desmosomal disruption and suprabasal acantholysis. Tight junctions (TJ) are located in the granular cell layer in normal skin and contribute to the epidermal barrier. Aberrations in the epidermal differentiation, such as in psoriasis, have been shown to lead to changes in the expression of TJ components. Our aim was to elucidate the expression and dynamics of the TJ proteins during the disruption of desmosomes in HHD and DD lesions. Indirect immunofluorescence and avidin-biotin labeling for TJ, desmosomal and adherens junction proteins, and subsequent analyses with the confocal laser scanning microscope were carried out on 14 HHD and 14 DD skin samples. Transepidermal water loss (TEWL) was measured in normal and lesional epidermis of nine HHD and eight DD patients to evaluate the function of the epidermal barrier in HHD and DD skin. The localization of TJ proteins claudin-1, claudin-4, ZO-1, and occludin in perilesional HHD and DD epidermis was similar to that previously described in normal skin. In HHD lesions the tissue distribution of ZO-1 expanded to the acantholytic spinous cells. In agreement with previous findings, desmoplakin was localized intracellularly. In contrast claudin-1 and ZO-1 persisted in the cell-cell contact sites of acantholytic cells. TEWL was increased in the lesional skin. The current results suggest that TJ components follow different dynamics in acantholysis of HHD and DD compared to desmosomal and adherens junction proteins.
黑利-黑利病（HHD）和达里埃病（DD）是由钙（2+）-ATP酶突变引起的，最终导致桥粒破坏和基底层上棘层松解。紧密连接（TJ）位于正常皮肤的颗粒细胞层，有助于形成表皮屏障。已表明，表皮分化异常，如在银屑病中，会导致紧密连接成分表达的改变。我们的目的是阐明在HHD和DD病变中桥粒破坏过程中紧密连接蛋白的表达和动态变化。对14例HHD和14例DD皮肤样本进行了紧密连接、桥粒和黏着连接蛋白的间接免疫荧光和抗生物素蛋白-生物素标记，随后用共聚焦激光扫描显微镜进行分析。测量了9例HHD和8例DD患者正常和病变表皮的经表皮水分流失（TEWL），以评估HHD和DD皮肤中表皮屏障的功能。紧密连接蛋白claudin-1、claudin-4、ZO-1和闭合蛋白在HHD和DD病变周围表皮中的定位与先前在正常皮肤中描述的相似。在HHD病变中，ZO-1的组织分布扩展到棘层松解的棘细胞。与先前的发现一致，桥粒斑蛋白定位于细胞内。相比之下，claudin-1和ZO-1在棘层松解细胞的细胞-细胞接触部位持续存在。病变皮肤中的TEWL增加。目前的结果表明，与桥粒和黏着连接蛋白相比，紧密连接成分在HHD和DD的棘层松解过程中遵循不同的动态变化。
