Slug/Snai2 is a downstream mediator of epidermal growth factor receptor-stimulated reepithelialization.
Slug/Snai2 is a downstream mediator of epidermal growth factor receptor-stimulated reepithelialization.
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DOI：
10.1038/jid.2008.222
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发表时间：
2009-02
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影响因子：
--
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中科院分区：
文献类型：
--
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许多肽生长因子，包括表皮生长因子受体（EGFR）配体，在体内和体外加速伤口上皮再生。此外，表皮生长因子受体的表达在伤口边缘短暂增加，表明这种受体在伤口修复中的积极作用。在皮肤伤口的再上皮化过程中，角质形成细胞表现出类似于上皮-间充质转化（EMT）的表型可塑性。转录因子鼻涕虫是EMT在发展过程中的一个调节器，我们以前报道过鼻涕虫的表达是升高的角质形成细胞接壤的皮肤伤口在体内，体外和体外。在这项研究中，我们提供的证据表明，鼻涕虫的表达是必要的EGFR刺激的再上皮化反应。EGF诱导Slug表达，对EGFR活化的反应比对其他受体酪氨酸激酶配体的反应更强烈。表皮生长因子受体刺激的再上皮化是高度依赖于蛞蝓，证明了缺乏表皮生长因子刺激的生长在外植体来自蛞蝓无效小鼠。在体外刺激异位鼻涕虫表达的上皮再生没有受到损害的EGFR催化活性的抑制剂，这表明鼻涕虫是这种EGFR刺激的反应的下游介质。我们的研究结果提供的证据表明，鼻涕虫是一个重要组成部分的途径，导致表皮生长因子受体介导的上皮生长。
Many peptide growth factors, including epidermal growth factor receptor (EGFR) ligands, accelerate wound reepithelialization in vivo and in vitro. Furthermore, EGFR expression is transiently increased at wound margins, suggesting an active role for this receptor in wound repair. During reepithelialization of cutaneous wounds, keratinocytes display a phenotypic plasticity resembling aspects of epithelial-mesenchymal transformation (EMT). The transcription factor Slug is a regulator of EMT during development, and we reported previously that Slug expression is elevated in keratinocytes bordering cutaneous wounds in vivo, ex vivo, and in vitro. In this study we provide evidence that Slug expression is necessary for an EGFR-stimulated reepithelialization response. EGF induces Slug expression and the response to EGFR activation is more robust than to other receptor tyrosine kinase ligands. EGFR-stimulated reepithelialization is highly dependent on Slug, as demonstrated by the absence of EGF-stimulated outgrowth in explants derived from Slug null mice. In vitro reepithelialization stimulated by ectopic Slug expression was not impaired by an inhibitor of EGFR catalytic activity suggesting that Slug is a downstream mediator of this EGFR-stimulated response. Our findings provide evidence that Slug is an essential component of the pathway leading to EGFR-mediated epithelial outgrowth.
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