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Role of ADAM family in normal human epidermal keratinocytes

ADAM家族在正常人表皮角质形成细胞中的作用

基本信息

批准号：
13670890
负责人：
SHIRAKATA Yuji
金额：
$ 2.3万
依托单位：
Ehime University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670890/
关键词：
ADAM mRNA adenovirus vector dominant negative real time PCR keratinocyte psoriasis vulgaris psoriasis vulgaris

项目摘要

ADAM family is transtmembrane protein that shares a disintegrin domain and metalloproteinase domain. To date, more than 30 members have been identified, although their role and regulation in normal human keratinocytes have not been fully determined. In order to assess whether ADAM family play an important role for keratinocyte proliferation and differentiation, we investigated their expression in normal human keratinocytes. We constructed Taqman probe for 19 ADAM family members. Total RNA was harvested from normal human keratinocytes under serum free condition, and then the expression level was determined by real time polymerase chain reaction. Keratinocyte express 15 ADAM family members at proliferating phase, and ADAM9 was upregulated by the addition of EGF. To further characterize the involvement of ADAM in skin disease, we investigated ADAM expression in lesional epidermis of psoriasis vulgaris, a hyperproliferative disorder. Epidermis was separated by heat activation from 13 skin samples from psoriasis vulgaris and 11 skin samples from normal healthy skin, and total RNA was extracted. ADAM expression was determined by real time PCR. There is no difference about ADAM12, 21, TS3, TS4, TS5 and TS6 expression between psoriasis vulgaris and normal health skin, whereas ADAM10, 17, 20 and 28 were downregulated in psoriatic epidermis, and ADAM30 was upregulated in psoriatic epidermis. ADAM15 was dramatically downregulated in psoriatic epidermis. Furthermore, ADAM19 and ADAMTS7 were significantly upregulated in psoriatic epidermis. Taking together, we demonstrated that normal human keratinocytes express more than 15 ADAM families, and ADAM family might be involved in the pathogenesis of psoriasis vulgaris.

ADAM家族是一种跨膜蛋白，具有去整合素结构域和金属蛋白酶结构域。到目前为止，已经确定了30多个成员，尽管它们在正常人类角质形成细胞中的作用和调控还没有完全确定。为了探讨ADAM家族在角质形成细胞的增殖和分化中是否起重要作用，我们研究了其在正常人角质形成细胞中的表达。我们为19个Adam家族成员构建了Taqman探测器。在无血清条件下从正常人角质形成细胞中提取总RNA，用实时定量聚合酶链式反应检测其表达水平。角质形成细胞在增殖期表达15个ADAM家族成员，加入EGF后ADAM9表达上调。为了进一步研究ADAM在皮肤病中的作用，我们研究了ADAM在寻常型银屑病(一种增生性疾病)皮损中的表达。用热激活法从13例寻常型银屑病患者皮肤和11例正常人皮肤标本中分离表皮，提取总RNA。用实时荧光定量聚合酶链式反应检测ADAM的表达。ADAM12、21、TS3、TS4、TS5、TS6在寻常型银屑病皮损中的表达与正常皮肤无明显差异，而ADAM10、17、20、28在银屑病皮损中表达下调，ADAM30在银屑病皮损中表达上调。ADAM15在银屑病表皮中的表达显著下调。此外，ADAM19和ADAMTS7在银屑病表皮中显著上调。综上所述，我们证实正常人角质形成细胞表达超过15个ADAM家族，并且ADAM家族可能参与寻常型银屑病的发病机制。