KLF7对周围神经损伤后施万细胞髓鞘形成和分化作用及miRNA靶向调控

转录因子如何调控神经损伤后施万细胞的髓鞘形成和分化是目前研究热点。本课题组首次发现核转录因子KLF7参与周围神经损伤的修复，但关于其调控机制，迄今国内外尚无报道。预实验中我们发现KLF7转染能够促进周围神经损伤后轴突再生、髓鞘形成和功能恢复。我们推测KLF7在神经损伤后施万细胞髓鞘形成和分化过程中起关键性调节作用，这可能是周围神经再生的一个新机制。为证实这一假说，我们将构建KLF7基因敲除小鼠模型，采用基因芯片杂交、分子生物学、流式细胞仪等技术，从细胞水平、分子水平和整体水平，以施万细胞髓鞘形成和分化及相关基因调控等为切入点，阐明KLF7对施万细胞的调节机制。同时首次筛选和确认与周围神经损伤后KLF7调控相一致的miRNA，确认其作用位点，从miRNA水平阐明KLF7促周围神经再生的作用机制，为进一步研究周围神经再生的分子机制、发现新型miRNA作用靶点供新的研究思路和实验基础。

How transcription factors control cellular myelination and maintain differentiation is currently of great interest. Krüppel-like Factor 7 engineered for transcriptional activation promotes axon regeneration in the adult corticospinal tract. Little is known about the transcriptional KLF7control of changes in SC injury. Here, we use mice with selective inactivation of the transcription factor KLF7 in SCs to show that KLF7 is a global regulator of the SC injury response that specifies the characteristic gene expression, structure, determines the expression of trophic factors, adhesion molecules,the formation of regeneration tracks and myelin clearance and controls the distinctive regenerative potential of peripheral nerves.We performed expression profiling studies and identified miRNAs differentially expressed during peripheral myelination. Our results indicate that miRNA play an important regulatory role in the promotion of SC myelination and differentiation by targeting to KLF7,providing novel insights into the roles of miRNAs in nerve injury and repair.