Department of Medical Microbiology and Immunology, University of Wisconsin-Madison, Madison, United States.
Cellular and Molecular Biology Graduate Program, University of Wisconsin-Madison, Madison, United States.
Elife. 2024 Aug 29;13:RP94995. doi: 10.7554/eLife.94995.
Epithelial damage leads to early reactive oxygen species (ROS) signaling, which regulates sensory neuron regeneration and tissue repair. How the initial type of tissue injury influences early damage signaling and regenerative growth of sensory axons remains unclear. Previously we reported that thermal injury triggers distinct early tissue responses in larval zebrafish. Here, we found that thermal but not mechanical injury impairs sensory axon regeneration and function. Real-time imaging revealed an immediate tissue response to thermal injury characterized by the rapid Arp2/3-dependent migration of keratinocytes, which was associated with tissue scale ROS production and sustained sensory axon damage. Isotonic treatment was sufficient to limit keratinocyte movement, spatially restrict ROS production, and rescue sensory neuron function. These results suggest that early keratinocyte dynamics regulate the spatial and temporal pattern of long-term signaling in the wound microenvironment during tissue repair.
上皮损伤会导致早期活性氧（ROS）信号转导，从而调节感觉神经元的再生和组织修复。初始组织损伤类型如何影响感觉轴突的早期损伤信号和再生生长仍不清楚。我们之前的研究表明，热损伤会在幼虫斑马鱼中引发不同的早期组织反应。在这里，我们发现热损伤而不是机械损伤会损害感觉轴突的再生和功能。实时成像显示，热损伤会立即引发组织反应，表现为角蛋白细胞的快速 Arp2/3 依赖性迁移，这与组织尺度 ROS 的产生和持续的感觉轴突损伤有关。等渗处理足以限制角蛋白细胞的运动，在空间上限制 ROS 的产生，并挽救感觉神经元的功能。这些结果表明，早期角蛋白细胞动力学调节组织修复过程中伤口微环境中长期信号的空间和时间模式。
