lncRNA BC098786和BC088259调控坐骨神经再生的机制

Nerve regeneration is a complex biological phenomenon incorporating multiple cells, growth factors and an extracellular matrix. Schwann cells are the prevalent cell type in the myelinated axon and play important roles in regulating nerve regenerative properties. Long noncoding RNAs (lncRNAs) are considered to be longer than 200 nucleotides, and have no protein-coding capacity. Numerous lncRNAs have speci?c biological functions, which regulate gene expression at the level of chromatin modification, transcription and post-transcriptional processing. We analyzed the changes in lncRNA and mRNA expression using microarray in the proximal stumps of the nerve, following sciatic nerve resection. A coexpression network of dys-regulated lncRNAs and coding genes was constructed. The present study is to elucidate vital roles for lncRNA BC098786 and BC088259 in controlling the remodeling of Schwann cells through the functional mediator during nerve injury and repair. We further determine the outcome of repairing rat sciatic nerve defects with BC098786/BC088259 modified Schwann cells as support cells, and evaluate the use of lncRNAs as new targets.

坐骨神经损伤后修复与再生的过程受到很多分子和细胞的调控，而Schwann细胞在神经损伤后的变性和再生中有着非常重要的作用。Long noncoding RNA (lncRNA)是一类长度大于200 nt，不编码蛋白的基因转录产物,主要通过表观遗传学、转录调控及转录后调控等层面实现对基因表达的调控，在多种生物学过程中发挥重要作用。前期系统性分析了大鼠坐骨神经缺损后不同时间点缺损近端神经lncRNA表达谱和mRNA表达谱，完成差异lncRNA与基因的共表达网络分析。本课题将进一步分析lncRNA BC098786和BC088259通过影响Schwann细胞的生物学行为调控髓鞘的形成，而这种作用是通过其靶基因参与的；并用BC098786/BC088259修饰的Schwann细胞作为种子细胞在体观察大鼠缺损坐骨神经修复的效果，探讨lncRNA作为新靶点的应用价值。

Long noncoding RNA (lncRNA)是一类长度大于200 nt，不编码蛋白的基因转录产物，主要通过表观遗传学、转录调控及转录后调控等层面实现对基因表达的调控，在多种生物学过程中发挥重要作用。我们首次通过高通量筛选及生物信息学分析发现大鼠坐骨神经夹伤后损伤神经中存在758个差异表达的lncRNA和6类显著性的主流表达趋势。lncRNA BC088259损伤后表达上调，主要定位于细胞浆，RNA-pull down筛选、RIP实验等验证BC088259与骨架蛋白Vimentin结合，促进Schwann细胞的迁移；lncRNA TNXA-PS1损伤后表达下调，主要定位于细胞浆，以ceRNA作用方式结合miR-24/miR-152，进一步结合Dusp1抑制Schwann细胞的激活。该方面研究扩充了非编码RNA网络在周围神经再生中的调控体系。