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热休克蛋白 27 作为预测人体皮肤和重建器官型皮肤模型中皮肤刺激的生物标志物。

HSP27 as a biomarker for predicting skin irritation in human skin and reconstructed organotypic skin model.

机构信息

Institute of Biomedicine and National Engineering Research Center of Genetic Medicine, Jinan University, Guangzhou 510632, China.

Guangzhou Women and Children's Medical Center, Guangzhou 510623, China.

出版信息

Toxicol Lett. 2014 Apr 21;226(2):124-31. doi: 10.1016/j.toxlet.2014.01.043. Epub 2014 Feb 3.

Abstract

In vitro alternative tests aiming at replacing the traditional animal test for predicting the irritant potential of chemicals have been developed, but the assessing parameters or endpoints are still not sufficient. To discover novel endpoints for skin irritation responses, 2DE-based proteomics was used to analyze the protein expression in human skin exposed to sodium lauryl sulfate (SLS) following the test protocol of the European Centre for the Validation of Alternative Methods (ECVAM) in the present study. HSP27 was up-regulated most significantly among the eight identified proteins, consistent with our previous reports. Acid and basic chemicals were applied on human skin for further validation and results showed that the up-regulated expression of HSP27 was induced in 24h after the exposure. Skin-equivalent constructed with fibroblasts, basement membrane and keratinocytes was used to investigate the potential of HSP27 as a biomarker or additional endpoint for the hazard assessment of skin irritation. Our skin-equivalent (Reconstructed Organotypic Skin Model, ROSM) had excellent epidermal differentiation and was suitable for the skin irritation test. HSP27 also displayed an up-regulated expression in the ROSM in 24h after the irritants exposure for 15min. All these results suggest that HSP27 may represent a potential marker or additional endpoint for the hazard assessment of skin irritation caused by chemical products.

摘要

已经开发出了旨在替代传统动物试验以预测化学品刺激性的体外替代试验,但评估参数或终点仍然不足。为了发现皮肤刺激性反应的新终点,本研究采用基于 2-DE 的蛋白质组学技术,根据欧洲替代方法验证中心 (ECVAM) 的试验方案,分析人类皮肤在暴露于十二烷基硫酸钠 (SLS) 后的蛋白表达。在鉴定出的 8 种蛋白中,HSP27 的上调最为显著,与我们之前的报告一致。本研究还进一步验证了酸和碱性化学品对人体皮肤的影响,结果表明,暴露 24 小时后 HSP27 的表达上调。本研究使用构建的含有成纤维细胞、基底膜和角质形成细胞的皮肤等效物来研究 HSP27 作为皮肤刺激性危害评估的生物标志物或附加终点的潜力。我们的皮肤等效物(重建的器官型皮肤模型,ROSM)具有良好的表皮分化能力,适合进行皮肤刺激性试验。在暴露 15 分钟后,HSP27 在 ROSM 中的表达在 24 小时内也上调。所有这些结果表明,HSP27 可能代表化学产品引起皮肤刺激性危害评估的潜在标志物或附加终点。

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