Department of Cell and Systems Biology, University of Toronto, Toronto, ON M5S 3G5, Canada; Ted Rogers Centre for Heart Research, University of Toronto, Toronto, ON M5G 1M1, Canada.
Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 1X8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Cell Rep. 2021 Oct 19;37(3):109874. doi: 10.1016/j.celrep.2021.109874.
Embryos repair wounds rapidly, with no inflammation or scarring, in a process that involves polarization of the actomyosin cytoskeleton. Actomyosin polarization results in the assembly of a contractile cable around the wound that drives wound closure. Here, we demonstrate that a contractile actomyosin cable is not sufficient for rapid wound repair in Drosophila embryos. We show that wounding causes activation of the serine/threonine kinase p38 mitogen-activated protein kinase (MAPK) in the cells adjacent to the wound. p38 activation reduces the levels of wound-induced reactive oxygen species in the cells around the wound, limiting wound size. In addition, p38 promotes an increase in volume in the cells around the wound, thus facilitating the collective cell movements that drive rapid wound healing. Our data indicate that p38 regulates cell volumes through the sodium-potassium-chloride cotransporter NKCC1. Our work reveals cell growth and cell survival as cell behaviors critical for embryonic wound repair.
胚胎在修复伤口时速度很快，不会发生炎症或形成疤痕，这个过程涉及到肌动球蛋白细胞骨架的极化。肌动球蛋白的极化导致围绕伤口形成一个收缩性电缆，从而驱动伤口闭合。在这里，我们证明了收缩性的肌动球蛋白电缆对于果蝇胚胎的快速伤口修复是不够的。我们发现，伤口会导致丝氨酸/苏氨酸激酶 p38 有丝分裂原激活的蛋白激酶 (MAPK) 在伤口附近的细胞中被激活。p38 的激活减少了伤口周围细胞中诱导的活性氧物质的水平，从而限制了伤口的大小。此外，p38 促进了伤口周围细胞体积的增加，从而促进了驱动快速伤口愈合的细胞集体运动。我们的数据表明，p38 通过钠钾氯共转运蛋白 NKCC1 调节细胞体积。我们的工作揭示了细胞生长和细胞存活作为胚胎伤口修复的关键细胞行为。
