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丝氨酸蛋白酶抑制剂 SCCA1 的上调与表皮屏障破坏有关。

Up-regulation of serpin SCCA1 is associated with epidermal barrier disruption.

机构信息

Shiseido Research Center, 2-12-1 Fukuura, Kanazawa-ku, Yokohama 236-8643, Japan.

出版信息

J Dermatol Sci. 2010 Feb;57(2):95-101. doi: 10.1016/j.jdermsci.2009.09.004. Epub 2010 Jan 7.

DOI:10.1016/j.jdermsci.2009.09.004
PMID:20089382
Abstract

BACKGROUND

Parakeratosis, the persistent presence of nuclei in the stratum corneum (SC) is associated with serious disruption of skin barrier function. Squamous cell carcinoma antigen 1 (SCCA1) is strongly up-regulated in inflamed and parakeratotic skin.

OBJECTIVE

To find a biochemical marker for the SC barrier disruption, especially the disruption associated with parakeratosis.

METHODS

An ELISA assay system was established to quantify SCCA1 in the extract of tape-stripped cornified cells. Transepidermal water loss (TEWL) and other skin parameters were measured and compared with the amount of SCCA1. Localization of SCCA1 was investigated immunohistochemically in various skin diseases with parakeratosis. Nuclei and SCCA1 on the skin surface were detected by staining of corniocytes collected on an adhesive-coated slide glass.

RESULTS

SCCA1 showed strong up-regulation in lesional skin with psoriasis (466-fold), hayfever skin caused by Japanese ceder pollen (232-fold) and sun-exposed skin of healthy individuals (90-fold) compared to their normal sun-protected skin. The increased levels of SCCA1 were well correlated with increased values of TEWL and the number of parakeratotic cells in the SC. Furthermore, subjects with high levels of SCCA1 in the epidermis were more susceptible to barrier disruption by external stimuli, and this was accompanied with a further increase of SCCA1. We confirmed that localization of SCCA1 was limited to parakeratotic areas by using the skin surface staining technique. Immunohistochemical study also demonstrated that SCCA1 was always present at high levels in parakeratotic epidermis.

CONCLUSION

All of our findings indicate that SCCA1 plays an important role in the induction of epidermal barrier disruption. SCCA1 may be a critical determinant of barrier function in the epidermis.

摘要

背景

角化不全是指角质层中持续存在细胞核,与皮肤屏障功能严重受损有关。鳞状细胞癌抗原 1(SCCA1)在炎症和角化不全的皮肤中强烈上调。

目的

寻找角质层屏障破坏的生化标志物,特别是与角化不全相关的破坏。

方法

建立了一种酶联免疫吸附试验(ELISA)检测系统,用于定量测定胶带剥离的角化细胞提取物中的 SCCA1。测量并比较经皮水分丢失(TEWL)和其他皮肤参数与 SCCA1 的量。用免疫组织化学方法研究各种角化不全性皮肤病中 SCCA1 的定位。通过染色收集在粘性涂层载玻片上的角质细胞,检测皮肤表面的 SCCA1 和细胞核。

结果

与正常防晒皮肤相比,银屑病病变皮肤(466 倍)、日本雪松花粉引起的花粉症皮肤(232 倍)和健康个体暴露于阳光的皮肤(90 倍)中 SCCA1 表达明显上调。SCCA1 水平的升高与 TEWL 值的升高和角质层中角化不全细胞数量的增加密切相关。此外,表皮中 SCCA1 水平较高的受试者对外部刺激引起的屏障破坏更为敏感,并且 SCCA1 进一步增加。我们通过使用皮肤表面染色技术证实了 SCCA1 的定位仅限于角化不全区域。免疫组织化学研究还表明,角化不全的表皮中 SCCA1 始终高表达。

结论

我们所有的发现都表明 SCCA1 在诱导表皮屏障破坏中起重要作用。SCCA1 可能是表皮屏障功能的关键决定因素。

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