The astrocytic response to injury is characterized on the cellular level, but our understanding of the molecular mechanisms controlling the cellular processes is incomplete. The astrocytic response to injury is similar to wound-healing responses in non-neural tissues that involve epithelial-to-mesenchymal transitions (EMTs) and upregulation in ZEB transcription factors. Here we show that injury-induced astrogliosis increases EMT-related genes expression, including Zeb2, and long non-coding RNAs, including Zeb2os, which facilitates ZEB2 protein translation. In mouse models of either contusive spinal cord injury or transient ischemic stroke, the conditional knockout of Zeb2 in astrocytes attenuates astrogliosis, generates larger lesions, and delays the recovery of motor function. These findings reveal ZEB2 as an important regulator of the astrocytic response to injury and suggest that astrogliosis is an EMT-like process, which provides a conceptual connection for the molecular and cellular similarities between astrogliosis and wound-healing responses in non-neural tissue.

星形胶质细胞对损伤的反应是在细胞水平上表征的，但是我们对控制细胞过程的分子机制的理解是不完整的。星形胶质细胞对损伤的反应类似于非神经组织中的伤口愈合反应，涉及上皮-间充质转化（EMT）和ZEB转录因子上调。在这里，我们显示了损伤诱导的星形胶质增生增加了与EMT相关的基因表达，包括Zeb2，以及长的非编码RNA，包括Zeb2os，这促进了ZEB2蛋白的翻译。在任一挫伤性脊髓损伤或短暂缺血性中风，的条件性敲除的小鼠模型ZEB2星形胶质细胞中的淀粉样蛋白可减轻星形胶质细胞增生，产生更大的病变，并延迟运动功能的恢复。这些发现揭示了ZEB2是星形胶质细胞对损伤的重要调节器，并表明星形胶质细胞增生是一种类似于EMT的过程，为星形胶质细胞增生和非神经组织伤口愈合反应之间的分子和细胞相似性提供了概念上的联系。