Methyl CpG binding protein 2 (MeCP2) is involved in nerve regeneration following ischemic stroke, but the related mechanism remains unclear. Here, we found low MeCP2 expression in hippocampal tissues. Using functional analysis, we demonstrated that MeCP2 accelerated FOXO3a methylation and subsequently inhibited its expression, thus repressing the apoptosis of neuronal cells. Mechanistically, FOXO3a could bind to the promoter region of SPRY2, consequently inducing its transcription and promoting the expression of the downstream target gene ZEB1. Altogether, our study revealed that overexpression of MeCP2 can protect mice against ischemic brain injury via disruption of the FOXO3a/SPRY2/ZEB1 signaling axis. Our results identify ectopic expression of MeCP2 as a therapeutic target in ischemic stroke.

甲基 CpG 结合蛋白 2 (MeCP2) 参与缺血性脑卒中后的神经再生，但相关机制尚不清楚。在这里，我们发现海马组织中的 MeCP2 表达较低。使用功能分析，我们证明 MeCP2 加速 FOXO3a 甲基化并随后抑制其表达，从而抑制神经元细胞的凋亡。从机制上讲，FOXO3a 可以结合 SPRY2 的启动子区域，从而诱导其转录并促进下游靶基因 ZEB1 的表达。总之，我们的研究表明，MeCP2 的过表达可以通过破坏 FOXO3a/SPRY2/ZEB1 信号轴来保护小鼠免受缺血性脑损伤。我们的结果将 MeCP2 的异位表达确定为缺血性中风的治疗靶点。