转录因子ZXDC对脊髓损伤后脊髓下行固有束“功能性中继”调控及分子机制研究

脊髓下行固有束（DPST）的“功能性中继”作用是脊髓损伤（SCI）后功能重建的重要治疗靶点，我们首次发现：JAK2/STAT3作为KLF7的下游信号通路参与DPST轴突再生，转录因子ZXDC可正向调控KLF7及JAK2/STAT3表达，促进DPST轴突可塑性，因此推测ZXDC可能是调控轴突再生网络中的一个新型转录因子，通过KLF7及下游JAK2/STAT3信号通路调控DPST“功能性中继”作用，为证实这一假说，本研究从转录、细胞和整体水平首次阐明ZXDC→KLF7→JAK2/STAT3信号通路转录调控机制；明确ZXDC对DPST神经元细胞形态、生化特征及分子结构的调控；探讨ZXDC调控DPST“功能性中继”是否依赖于KLF7及JAK2/STAT3信号通路；分析ZXDC对CST/RST支配DPST“功能性中继”的调控机制。全面、深入地解析ZXDC对DPST“功能性中继”的生物学功能。

The“functional relay” of descending propriospinal tract (DPST) is an important therapeutic target for spinal cord injury (SCI). We firstly found that JAK2/STAT3 acted as downstream KLF7 signalling pathway was involved in DPST regeneration procession, transcription factor ZXDC can positively regulate the expression of KLF7 and JAK2/STAT3, and promotes DPST axon plasticity following SCI, which suggesting that ZXDC modulate DPST “functional relay” through regulating KLF7 and JAK2/STAT3 signaling pathway, ZXDC is a new regulatory factor in the complex network regulating DPST axon regeneration. To confirm this hypothesis, from the transcriptional, cell and overall levels, we explore the transcriptional regulation mechanism of ZXDC→KLF7→JAK2/STAT3 signaling pathway; To explicit the effect of ZXDC regulation the on cellular morphology, biochemical characteristics and molecular structure of DPST neurons; To clarify whether ZXDC regulation of DPST “functional relay” and functional reconstruction through regulating KLF7 and JAK2/STAT3 signaling pathway; To evaluate the regulation mechanism of ZXDC on the corticospinal tract (CST) and rubrospinal tracts (RST) dominate DPST “functional relay”, and alalysed the ZXDC biology function of ZXDC in DPST “functional relay” deeply and comprehensively.