The Galvanotactic Migration of Keratinocytes is Enhanced by Hypoxic Preconditioning.
The Galvanotactic Migration of Keratinocytes is Enhanced by Hypoxic Preconditioning.
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DOI：
10.1038/srep10289
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发表时间：
2015-05-19
影响因子：
4.6
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Guo X;Jiang X;Ren X;Sun H;Zhang D;Zhang Q;Zhang J;Huang Y
内源性电场（EF）引导的角质形成细胞向伤口中的迁移（趋电性）是伤口再上皮化中的重要步骤。损伤后立即发生的缺氧作为启动愈合过程的早期刺激;然而，这种作用的机制仍然难以捉摸。我们在这里表明，角质形成细胞的趋电迁移增强低氧预处理的结果增加的方向性，而不是角质形成细胞的运动性增加。这种增强是氧张力和预处理时间依赖性的，使用2%O2预处理6小时达到最大效果。低氧预处理（2%O_2，6小时）使趋电性阈值电压降低至< 25 mV/mm，而正常培养对照组的阈值电压在25 ~ 50 mV/mm之间。在划痕伤口单层试验中，其中所施加的EF是在默认的愈合方向，低氧预处理加速愈合的1.38倍，与对照条件相比。用N-乙酰半胱氨酸（NAC）清除诱导的ROS，可消除低氧预处理所增强的趋电性和加速愈合。我们的数据表明，缺氧在支持角质形成细胞趋电性中的一种新的和意料之外的作用。因此，增强细胞的趋电反应可能是一种临床上有吸引力的方法，以诱导改善伤口愈合。
The endogenous electric field (EF)-directed migration of keratinocytes (galvanotaxis) into wounds is an essential step in wound re-epithelialization. Hypoxia, which occurs immediately after injury, acts as an early stimulus to initiate the healing process; however, the mechanisms for this effect, remain elusive. We show here that the galvanotactic migration of keratinocytes was enhanced by hypoxia preconditioning as a result of the increased directionality rather than the increased motility of keratinocytes. This enhancement was both oxygen tension- and preconditioning time-dependent, with the maximum effects achieved using 2% O2 preconditioning for 6 hours. Hypoxic preconditioning (2% O2, 6 hours) decreased the threshold voltage of galvanotaxis to < 25 mV/mm, whereas this value was between 25 and 50 mV/mm in the normal culture control. In a scratch-wound monolayer assay in which the applied EF was in the default healing direction, hypoxic preconditioning accelerated healing by 1.38-fold compared with the control conditions. Scavenging of the induced ROS by N-acetylcysteine (NAC) abolished the enhanced galvanotaxis and the accelerated healing by hypoxic preconditioning. Our data demonstrate a novel and unsuspected role of hypoxia in supporting keratinocyte galvanotaxis. Enhancing the galvanotactic response of cells might therefore be a clinically attractive approach to induce improved wound healing.
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