Cornified Cell Envelope Formation of Psoriatic Keratinocytes

在分化的后期，表皮角质形成细胞在质膜下形成角化的细胞膜。在银屑病中，已知前体蛋白的表达模式错乱；总蛋白表达增加，氯化蛋白表达减少。应用光镜和电子显微镜免疫组织化学方法，比较正常和银屑病角化细胞包膜的形成。在正常表皮中，角化的细胞膜来自角化细胞的最深处，或在存在的情况下，来自过渡细胞，随着成熟，角化细胞的厚度增加并改变电子密度。银屑病表皮角化细胞包膜形成较早，角化层下方1~数个细胞。正常角化细胞包膜仅在非常早期呈包膜蛋白阳性，而银屑病角化细胞包膜显示持续的包膜包膜蛋白免疫反应。结果表明，在正常皮肤中，卷毛蛋白是主要的…角化细胞膜的更多成分仅在其组装的早期阶段。相反，银屑病皮肤角化细胞包膜的形成似乎是过早启动的，因为在成熟过程中，包膜蛋白仍然是角化细胞包膜的主要成分。转录增强因子1(TEF-1)与SV40增强子结合，是一种在包括角质形成细胞在内的各种细胞中表达的核蛋白。TEF-1蛋白在基底细胞层高表达。我们对构建的INV-CAT载体进行了活性分析，该载体是将该基因的5‘上游区域连接到CAT报告基因上构建的。将TEF-1表达载体与INV-CAT载体共转染，可显著提高INV-CAT启动子活性。GAL4-TEF-1载体通过GAL4激活域取代TEF-1DNA结合域构建而成。这表明TEF-1诱导的抑制是由于干扰/抑制了一种限制转录中介因子，该因子对总蛋白的表达是必不可少的。TEF-1依赖抑制总蛋白基因的表达可能解释了表皮中基础以上的总蛋白表达。表皮的结构不是由简单的增殖条件决定的，而是由表皮周转时间决定的(这既取决于细胞数量，也取决于增殖条件)。这与角化过程有关，角化过程需要一定的时间才能完成。利用这个概念，自然地描述了过度增殖的“牛皮癣样”表皮和低增殖的“萎缩性”表皮。较少

Epidermal keratinocytes form a cornified cell envelope beneath the plasma membrane during the late stages of differentiation. In psoriasis, the expression pattern of the precursor proteins is known to be deranged ; involucrin expression is increased and loricrin expression is decreased. Using light and electron microscopic immunohistochemistry, we compared normal and psoriatic cornified cell envelope formation. In normal epidermis.cornified cell envelopes were observed from the deepest cornified cells or when present, from the transitional cells, increasing in thickness and changing electron densities with maturation. In psoriatic epidermis, cornified cell envelope formation started earlier, one to several cells below the cornified layr. The normal cornified cell envelope was shown to be involucrin positive only at a very early stage, whereas psoriatic cornified cell envelope showed persistent involucrin immunoreactivity. The results suggest that in normal skin, involucrin is the major … More constituent of the cornified cell envelope only in its early stages of assembly. In contrast, cornified cell envelope formation seems to be initiated prematurely in psoriatic skin, were involucrin remains the major constituent of the cornified cell envelope during maturation.Transcriptional enhancer factor 1 (TEF-1), which binds to SV40 enhancer, is a nuclear protein expressed in various cells including keratinocytes. TEF-1 protein was shown to be highly expressed on the basal cell layr. We analyzed involucrin promoter activity of the INV-CAT vector, which was constructed by connecting the 5' upstream region of involucrin gene to the CAT reporter gene. Co-transfection of TEF-1 expression vector with INV-CAT vector significantly the INV-CAT promoter activity. The repression was also observed by transfection of the GAL4-TEF-1 vector, which was constructed by replacement of the TEF-1 DNA binding domain by the GAL4 activator domain. This suggests that TEF-1-induced repression is due to interference/squelching of a limiting transcriptional intermediary factor that is essential for involucrin expression. TEF-1 dependent-repression of involucrin gene expression might explain the suprabasal involucrin expression in the epidermis.The concept of epidermal architecture that depends on epidermal turnover time was established. The epidermal architecture is determined, not by a simple proliferative condition, but rather by an epidermal turnover time (that depends both on cell number as well as on the proliferative condition). This is in relation to 'keratinization process' that requires a definite time to be completed. Using the concept, hyperproliferative 'psoriasiform' epidermis and hypoproliferative 'atrophic' epidermis are naturally described. Less