Erk5 Controls Slug Expression and Keratinocyte Activation during Wound Healing
Erk5 Controls Slug Expression and Keratinocyte Activation during Wound Healing
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DOI：
10.1091/mbc.e07-10-1078
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发表时间：
2008-11-01
影响因子：
3.3
通讯作者：
Savagner, Pierre
中科院分区：
文献类型：
--
作者：
Arnoux, Valerie;Nassour, Mayssaa;Savagner, Pierre
皮肤创面愈合过程中的再上皮化涉及许多信号，这些信号导致基础角质形成细胞的激活、扩散和迁移，所有这些都与细胞-细胞黏附结构的松动有关。在这个过程中，转录因子Slug是必需的，而EGF处理人角质形成细胞可以激活ERK5的磷酸化，这与Slug的转录是一致的。因此，ERK5的异位激活导致slug mRNA水平的增加和创面愈合的加快，而角质形成细胞的迁移则被ERK5通路的抑制完全阻止。ERK5特异性shRNA的表达显著降低角质形成细胞中ERK5的水平，并显著降低角质形成细胞对EGF的运动反应，同时诱导Slug的表达。这些缺乏ERK5的角质形成细胞表现出改变的、更致密的形态，并伴随着桥粒组织的破坏。因此，他们表现出了一种改变的形成细胞聚集体的能力。这些结果表明，一种新的EGFR/ERK5/slug通路在EGF处理的角质形成细胞中控制细胞骨架组织和细胞运动。
Reepithelialization during cutaneous wound healing involves numerous signals that result in basal keratinocyte activation, spreading, and migration, all linked to a loosening of cell-cell adhesion structures. The transcription factor Slug is required for this process, and EGF treatment of human keratinocytes induced activating phosphorylation of Erk5 that coincides with slug transcription. Accordingly, ectopic activation of Erk5 led to increased Slug mRNA levels and faster wound healing, whereas keratinocyte migration was totally blocked by Erk5 pathway inhibition. Expression of a shRNA specific for Erk5 strongly diminished Erk5 levels in keratinocytes and significantly decreased their motility response to EGF, along with induction of Slug expression. These Erk5-deprived keratinocytes showed an altered, more compact morphology, along with disruption of desmosome organization. Accordingly, they displayed an altered ability to form cell aggregates. These results implicate a novel EGFR/Erk5/Slug pathway in the control of cytoskeleton organization and cell motility in keratinocytes treated with EGF.