Plasma membrane repair mechanisms are activated within seconds post-injury to promote rapid membrane resealing in eukaryotic cells and prevent cell death. However, less is known about the regeneration phase that follows and how cells respond to injury in the short-term. Here, we provide a genome-wide study into the mRNA expression profile of MCF-7 breast cancer cells exposed to injury by digitonin, a mild non-ionic detergent that permeabilizes the plasma membrane. We focused on the early transcriptional signature and found a time-dependent increase in the number of differentially expressed (> twofold, P < 0.05) genes (34, 114 and 236 genes at 20-, 40- and 60-min post-injury, respectively). Pathway analysis highlighted a robust and gradual three-part transcriptional response: (1) prompt activation of immediate-early response genes, (2) activation of specific MAPK cascades and (3) induction of inflammatory and immune pathways. Therefore, plasma membrane injury triggers a rapid and strong stress and immunogenic response. Our meta-analysis suggests that this is a conserved transcriptome response to plasma membrane injury across different cell and injury types. Taken together, our study shows that injury has profound effects on the transcriptome of wounded cells in the regeneration phase (subsequent to membrane resealing), which is likely to influence cellular status and has been previously overlooked.

质膜修复机制在受伤后几秒钟内被激活，以促进真核细胞中的快速膜重新密封并防止细胞死亡。然而，对于随后的再生阶段以及细胞如何在短期内对损伤做出反应，我们知之甚少。在这里，我们提供了对暴露于毛地黄皂苷损伤的 MCF-7 乳腺癌细胞的 mRNA 表达谱的全基因组研究，毛地黄皂苷是一种可渗透质膜的温和非离子去污剂。我们专注于早期转录特征，发现差异表达的数量随时间增加（> 两倍，P < 0.05) 基因（分别在受伤后 20、40 和 60 分钟有 34、114 和 236 个基因）。通路分析强调了稳健且渐进的三部分转录反应：(1) 立即早期反应基因的迅速激活，(2) 特定 MAPK 级联的激活和 (3) 炎症和免疫通路的诱导。因此，质膜损伤会引发快速而强烈的应激和免疫原性反应。我们的荟萃分析表明，这是对跨不同细胞和损伤类型的质膜损伤的保守转录组反应。综上所述，我们的研究表明，损伤对再生阶段（膜重新密封之后）受伤细胞的转录组有深远的影响，这可能会影响细胞状态，但之前一直被忽视。