Biophysics Program, Stanford University, Stanford, United States.
Department of Biology and Howard Hughes Medical Institute, University of Washington, Seattle, United States.
Elife. 2020 Nov 23;9:e62386. doi: 10.7554/eLife.62386.
The ability of epithelial tissues to heal after injury is essential for animal life, yet the mechanisms by which epithelial cells sense tissue damage are incompletely understood. In aquatic organisms such as zebrafish, osmotic shock following injury is believed to be an early and potent activator of a wound response. We find that, in addition to sensing osmolarity, basal skin cells in zebrafish larvae are also sensitive to changes in the particular ionic composition of their surroundings after wounding, specifically the concentration of sodium chloride in the immediate vicinity of the wound. This sodium chloride-specific wound detection mechanism is independent of cell swelling, and instead is suggestive of a mechanism by which cells sense changes in the transepithelial electrical potential generated by the transport of sodium and chloride ions across the skin. Consistent with this hypothesis, we show that electric fields directly applied within the skin are sufficient to initiate actin polarization and migration of basal cells in their native epithelial context in vivo, even overriding endogenous wound signaling. This suggests that, in order to mount a robust wound response, skin cells respond to both osmotic and electrical perturbations arising from tissue injury.
上皮组织在受伤后能够自我修复，这对动物的生命至关重要，但上皮细胞感知组织损伤的机制尚未完全阐明。在斑马鱼等水生生物中，受伤后渗透压的变化被认为是激活伤口反应的早期和有效因素。我们发现，除了感知渗透压外，斑马鱼幼虫的基底皮肤细胞在受伤后还能敏感地感知周围环境特定离子组成的变化，特别是伤口附近氯化钠的浓度。这种特定于氯化钠的伤口检测机制不依赖于细胞肿胀，而是暗示了一种细胞感知钠离子和氯离子跨皮肤运输产生的跨上皮电位变化的机制。与这一假设一致的是，我们表明，即使在体内，电场也可以直接施加在皮肤内，足以在其天然上皮环境中引发肌动蛋白的极化和基底细胞的迁移，甚至可以覆盖内源性伤口信号。这表明，为了做出强烈的伤口反应，皮肤细胞会对来自组织损伤的渗透压和电扰动做出反应。
