Cellular crowding influences extrusion and proliferation to facilitate epithelial tissue repair
Cellular crowding influences extrusion and proliferation to facilitate epithelial tissue repair
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DOI：
10.1091/mbc.e18-05-0295
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发表时间：
2019-07-22
影响因子：
3.3
通讯作者：
Eisenhoffer, George T.
中科院分区：
文献类型：
--
作者：
Franco, Jovany J.;Atieh, Youmna;Eisenhoffer, George T.
上皮性伤口愈合需要复杂的细胞重排和运动来恢复损伤后的组织结构和功能。虽然众所周知，机械力可以影响组织的形态发生和模式，但在组织修复过程中，损伤后产生的生物物理信号如何影响细胞行为尚不清楚。通过对活斑马鱼幼体上皮组织的延时共聚焦成像，我们提供了证据表明，在伤口闭合过程中，细胞拥挤的局部增加通过机械调节的拉伸激活离子通道（SACs）促进了非凋亡细胞的挤压。定向细胞向损伤部位的迁移促进了细胞数量的快速变化，并在长空间距离上产生细胞界面张力的变化。SAC活性的扰动导致挤压失败和组织密集区域的增殖增加。总之，我们得出结论，局部细胞数量在决定促进伤口愈合和组织修复的细胞行为中起关键作用。
Epithelial wound healing requires a complex orchestration of cellular rearrangements and movements to restore tissue architecture and function after injury. While it is well known that mechanical forces can affect tissue morphogenesis and patterning, how the biophysical cues generated after injury influence cellular behaviors during tissue repair is not well understood. Using time-lapse confocal imaging of epithelial tissues in living zebrafish larvae, we provide evidence that localized increases in cellular crowding during wound closure promote the extrusion of nonapoptotic cells via mechanically regulated stretch-activated ion channels (SACs). Directed cell migration toward the injury site promoted rapid changes in cell number and generated shifts in tension at cellular interfaces over long spatial distances. Perturbation of SAC activity resulted in failed extrusion and increased proliferation in crowded areas of the tissue. Together, we conclude that localized cell number plays a key role in dictating cellular behaviors that facilitate wound closure and tissue repair.