Burke Neurological Institute, 785 Mamaroneck Avenue, White Plains, NY 10605, USA.
Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Charitéplatz 1, 10117 Berlin, Germany; Lobachevsky State University of Nizhny Novgorod, Gagarina Ave 23, 603950 Nizhny Novgorod, Russia.
Cell Rep. 2020 Jun 30;31(13):107834. doi: 10.1016/j.celrep.2020.107834.
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在细胞水平上具有特征性，但我们对控制细胞过程的分子机制的理解并不完整。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 转录因子的上调。在这里，我们表明，损伤诱导的星形胶质细胞增生增加了 EMT 相关基因的表达，包括 Zeb2，以及长非编码 RNA，包括 Zeb2os，这有助于 ZEB2 蛋白的翻译。在挫伤性脊髓损伤或短暂性脑缺血发作的小鼠模型中，星形胶质细胞中 Zeb2 的条件性敲除减弱了星形胶质细胞增生，导致更大的损伤，并延迟了运动功能的恢复。这些发现揭示了 ZEB2 是星形胶质细胞对损伤反应的重要调节因子，并表明星形胶质细胞增生是一种 EMT 样过程，这为星形胶质细胞增生和非神经组织中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。
