Re-epithelialization is a critical step in wound healing and results from the collective migration of keratinocytes. Previous work demonstrated that immobilized, but not soluble, epidermal growth factor (EGF) resulted in leader cell-specific activation of phospholipase C gamma 1 (PLCγ1) in HaCaT keratinocytes, and that this PLCγ1 activation was necessary to drive persistent cell migration. To determine the mechanism responsible for wound edge-localized PLCγ1 activation, we examined differences in cell area, cell-cell interactions, and EGF receptor (EGFR) localization between wound edge and bulk cells treated with vehicle, soluble EGF, or immobilized EGF. Our results support a multistep mechanism where EGFR translocation from the lateral membrane to the basolateral/basal membrane allows clustering in response to immobilized EGF. This analysis of factors regulating PLCγ1 activation is a crucial step toward developing therapies or wound dressings capable of modulating this signal and, consequently, cell migration.

中文翻译：

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角质形成细胞集体迁移过程中前导细胞 PLCγ1 的激活是由 EGFR 定位和聚集诱导的。

上皮再形成是伤口愈合的关键步骤，是角质形成细胞集体迁移的结果。先前的研究表明，固定但不可溶的表皮生长因子 (EGF) 会导致 HaCaT 角质形成细胞中磷脂酶 C γ 1 (PLCγ1) 的前导细胞特异性激活，并且这种 PLCγ1 激活对于驱动持续的细胞迁移是必要的。为了确定伤口边缘局部 PLCγ1 激活的机制，我们检查了伤口边缘和用载体、可溶性 EGF 或固定化 EGF 处理的大块细胞之间的细胞面积、细胞间相互作用和 EGF 受体 (EGFR) 定位的差异。我们的结果支持多步骤机制，其中 EGFR 从侧膜易位至基底外侧/基底膜，允许响应固定化 EGF 而聚集。对调节 PLCγ1 激活的因素的分析是开发能够调节该信号并从而调节细胞迁移的疗法或伤口敷料的关键一步。