The role of protease in pathogenesis of psoriasis

蛋白酶在银屑病发病机制中的作用

• 批准号: 08670984
• 负责人: TAKAMORI Kenji
• 金额: $ 1.47万
• 依托单位: Juntendo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08670984/
• 关键词: psoriasis; cell cycle; keratinocyte; keratinazation; proteasome; cyclin; ケラチノサイト; プロテアーム

It is well known that epidermal cell cycle in involved skin of patient with psoriasis is shortend remarkably. The shortening of the epidermal cell cycle is an important event in the pathogenesis of psoriasis. However the mechanisms of the shortening of cell cycle are not obscure. In this report , we decided at first the distribution of non-lysosomal proteinase, proteasome and cyclin in skin, and then investigated the role of proteasome in epidermal keratinization.1. Distribution of proteasome in skin Imniunochemical staining showed considerably increased expression of proteasome in the cytoplasm and the nuclei in normal skin and psoriasis skin. Proteasome activity also showed highest activity in living layer(granular - spinous layer).2. Distribution of cyclin protein Cyclin A was not stained in normal epidermis, however, stained stained strongly in psoriasis epidermis. Cyclin D was not detected in normal and psoriasis epidermis.3. The role of proteasome in keratinazation Proteasome and proteasome mRNA increased time dependently in proportion to the degree of keratinazation.These results suggest that proteasome is related to the keratinazatio and cyclin A is involved in the proliferation of epidermis.

众所周知，银屑病患者皮损表皮细胞周期明显缩短。表皮细胞周期的缩短是银屑病发病机制中的重要事件。然而，细胞周期缩短的机制并不模糊。本研究首先确定了非溶酶体蛋白酶、蛋白酶体和细胞周期蛋白在皮肤中的分布，进而探讨了蛋白酶体在表皮角化中的作用.蛋白酶体在皮肤中的分布免疫组化染色显示，正常皮肤和银屑病皮肤中蛋白酶体在细胞质和细胞核中的表达明显增加。蛋白酶体活性在活层（颗粒层-棘层）中也表现出最高活性.细胞周期蛋白Cyclin A在正常表皮中不表达，而在银屑病表皮中表达较强。Cyclin D在正常人和银屑病患者中均未检测到.蛋白酶体在表皮角化中的作用蛋白酶体和蛋白酶体mRNA随角化程度的增加呈时间依赖性增加，提示蛋白酶体与角化有关，细胞周期蛋白A参与表皮的增殖。