低分化状态的维持是创缘新生表皮的重要特征，是决定表皮细胞移行表型和运动性的关键。我们首次发现，创缘电场具有抑制表皮分化的重要作用，但机制不清楚。基于E-cadherin介导表皮分化的认识，结合工作基础，本研究提出电场信号经由EGFR/ERK/Snail途径，抑制E-cadherin转录，从而抑制表皮分化的假设，拟首先从体内外水平进一步明确电场抑制表皮细胞分化的作用，继而阐明E-cadherin表达及其介导的分化途径受抑是其重要机制；采用基因沉默等技术，揭示EGFR/ERK激活、上调Snail的转录抑制活性是E-cadherin表达受抑的关键；从表达到分布，探寻ERK调节Snail的可能环节与分子基础；最后，利用EGFR突变体转基因小鼠在体验证创缘电场抑制表皮分化的作用机制和意义。研究对揭示创面表皮分化调节新机制，创新电场促上皮化作用新理论，深化创面愈合乃至创面难愈机制的认识，具有重要意义。

The maintenance of low differentiation is an important feature of neonatal epidermis, and acts as the key to determine the migratory phenotype and motility of keratinocytes during wound reepithelialization. We found in vivo for the first time that wound endogenous electric field is an important signal to inhibit epidermal differentiation, but the mechanism is not clear. Based on a critical role for E-cadherin in mediating epidermal differentiation that has been well identified previously and our current findings, we here proposes a hypothesis that electric field signal inhibits E-cadherin transcription via the EGFR/ERK/Snail pathway, thereby inhibiting keratinocyte differentiation. We firstly intend to further confirm a role of electric field in keratinocyte differentiation in vivo and in vitro, and then elucidate that the suppressed E-cadherin and its mediated differentiation pathways accounts for the low differentiation of keratinocyte induced by electric field. Using techniques such as gene silencing et al., we plan to reveal that EGFR/ERK activation and up-regulation of transcription inhibitory activity of Snail are the key signal mechanisms for E-cadherion downregulation, and further check out how ERK regulates Snail from its transcription to intracellular distribution, and which molecular downstream of ERK responsible for the direct interaction with Snail. Finally, by using EGFR mutant mice, we intend to verify the signal mechanisms responsible for wound endogenous electric field suppressed epidermal differentiation in vivo. Therefore, this study would be of great significance in revealing a new mechanism of epidermal differentiation regulation, innovating the new theory for electric field promoting reepithelialization, and deepening our understanding on wound healing and even unhealing mechanisms.