Cornified Cell Envelope Formation of Psoriatic Keratinocytes

银屑病角质形成细胞的角化细胞包膜形成

• 批准号: 06454312
• 负责人: IIZUKA Hajime
• 金额: $ 4.8万
• 依托单位: Asahikawa Medical College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454312/
• 关键词: psoriasis; cornified cell envelope; involucrin; loricrin; turnover time; keratinization; AP-1; 乾癬; プロテインキナーゼC; 周辺帯(cornified cell envelope)

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

表皮角质形成细胞在分化的晚期阶段在质膜下形成角质形成细胞包膜。在银屑病中，已知前体蛋白的表达模式是紊乱的;外皮蛋白表达增加，兜甲蛋白表达减少。利用光镜和电镜免疫组化，我们比较了正常和银屑病皮质细胞包膜的形成。在正常表皮中，从最深的皮质细胞或过渡细胞（如果存在）观察到皮质细胞包膜，其厚度随成熟而增加，电子密度也随成熟而改变。银屑病患者表皮皮质细胞被膜的形成较早，在皮质层下方有1 ~数个细胞。正常皮质细胞包膜仅在非常早期呈外皮蛋白阳性，而银屑病皮质细胞包膜呈持续外皮蛋白免疫反应。结果表明，在正常皮肤中，外皮蛋白是主要的 ...更多信息 只有在组装的早期阶段，才能形成皮质细胞的包膜。与此相反，银屑病皮肤中皮质细胞被膜的形成似乎过早开始，其中外皮蛋白在成熟过程中仍然是皮质细胞被膜的主要成分。转录增强因子1（TEF-1）结合到SV 40增强子，是在包括角质形成细胞在内的多种细胞中表达的核蛋白。TEF-1蛋白在基底细胞层有高表达。我们分析了INV-CAT载体的外皮蛋白启动子活性，该载体通过将外皮蛋白基因的5'上游区连接到CAT报告基因而构建。将TEF-1表达载体与INV-CAT载体共转染后，INV-CAT启动子活性显著提高。通过转染GAL 4-TEF-1载体也观察到了抑制，所述载体通过用GAL 4激活结构域替换TEF-1 DNA结合结构域而构建。这表明TEF-1诱导的抑制是由于干扰/压制的限制性转录中介因子，这是必不可少的外皮蛋白的表达。TEF-1依赖的对外皮蛋白基因表达的抑制可能解释了外皮蛋白在表皮中的基底上表达，建立了表皮结构依赖于表皮更新时间的概念。表皮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（这取决于细胞数量以及增殖条件）。这与需要一定时间才能完成的“角质化过程”有关。使用该概念，过度增殖的“银屑病样”表皮和低增殖的“萎缩性”表皮被自然地描述。少

项目成果

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