HSP27 as a biomarker for predicting skin irritation in human skin and reconstructed organotypic skin model
HSP27 as a biomarker for predicting skin irritation in human skin and reconstructed organotypic skin model
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HSP27作为预测人类皮肤皮肤刺激的生物标志物并重建器官型皮肤模型
DOI：
10.1016/j.toxlet.2014.01.043
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发表时间：
2014-04-21
影响因子：
3.5
通讯作者：
Huang, Yadong
中科院分区：
文献类型：
--
作者：
Chen, Hongxia;Li, Shuhua;Huang, Yadong
体外替代试验旨在取代传统的动物试验来预测化学品的刺激性潜力，但评估参数或终点仍然不够。为了发现皮肤刺激反应的新终点，根据欧洲替代方法验证中心（ECVAM）的测试方案，使用基于2DE的蛋白质组学分析暴露于十二烷基硫酸钠（SLS）的人皮肤中的蛋白质表达。HSP27是上调最显着的八个确定的蛋白质，与我们以前的报告一致。将酸碱化学物质应用于人体皮肤进行进一步验证，结果显示，在暴露后24 h内诱导HSP 27的表达上调。使用由成纤维细胞、基底膜和角质形成细胞构建的皮肤等效物来研究H5P27作为皮肤刺激危险评估的生物标志物或额外终点的潜力。我们的皮肤等效物（重建器官型皮肤模型，ROSM）具有良好的表皮分化，适用于皮肤刺激试验。H5P27在刺激物暴露15 min后24 h的ROSM中表达上调。所有这些结果表明，H5P27可能代表化学产品引起的皮肤刺激的危险评估的潜在标志物或额外的终点。(C)2014爱思唯尔爱尔兰有限公司版权所有。
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 24 h after the exposure. Skin-equivalent constructed with fibroblasts, basement membrane and keratinocytes was used to investigate the potential of H5P27 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. H5P27 also displayed an up-regulated expression in the ROSM in 24 h after the irritants exposure for 15 min. All these results suggest that H5P27 may represent a potential marker or additional endpoint for the hazard assessment of skin irritation caused by chemical products. (C) 2014 Elsevier Ireland Ltd. All rights reserved.