UTX/microRNA24表观调控神经血管可塑性及其在脊髓损伤中的作用机制研究

Acute spinal cord injury (SCI) is a devastating traumatic disease in central nervous system. The posttraumatic lower neurovascular plasticity was the main factor in aggravating the SCI process. Thus, promoting neurovascular plasticity and improving its regeneration after SCI are the most effective way to enhance the spinal cord neurological function recovery. Studies have shown that epigenetic factors and microRNA will form a modification network governing the neurovascular plasticity. In our previous study, we found the posttraumatic differential expression of UTX and microRNA24, but the specific co-adjustment mechanism of them on neurovascular regeneration after SCI is unknown. In our current study, we aim to use in vitro cultured vascular/neural cell model and vascular and neuro-specific gene knockout mouse model, employ the three-dimensional imaging technology (SRμCT), combining with the chromatin immunoprecipitation, DNA methylation sequencing and luciferase test techniques respectively to reveal the effect of UTX/microRNA24 epigenetic regulation network on the neurovascular plasticity from the molecular, cellular and whole level and explain its underlying mechanism on neurovascular regeneration during the SCI process. All the above mentioned investigations are expected to establish the experimental evidence and theoretical basis for UTX/microRNA24 epigenetic regulation network to promote spinal cord neurological function recovery, and providing potential therapeutic targets in the management of SCI.

急性脊髓损伤（SCI）是一类严重的中枢神经系统创伤性疾病，创伤后神经血管可塑性降低是加重SCI的主要因素。因此，提高神经血管可塑性，促进其再生是改善SCI后脊髓神经功能的重要手段。研究表明，表观遗传因子与microRNA形成表观修饰网络，参与神经血管可塑性调控。我们前期研究发现，SCI后表观遗传因子UTX与microRNA24显著差异表达，但其在SCI中对神经血管再生的具体调控机制不明。本项目拟采用体外血管/神经细胞模型和体内血管/神经特异性基因敲除小鼠模型，利用先进的同步辐射三维成像技术、染色质免疫共沉淀、甲基化测序和荧光素酶实验等技术，从分子、细胞和整体水平揭示UTX/microRNA24表观调控网络对脊髓神经血管可塑性的调节作用，并阐述其在SCI中对神经血管再生的作用机理，为促进脊髓神经功能恢复，治疗SCI提供实验基础和理论依据。

急性脊髓损伤（SCI）是一类严重的中枢神经系统创伤性疾病，创伤后神经血管可塑性降低是加重SCI的主要因素。因此，提高神经血管可塑性，促进其再生是改善SCI后脊髓神经功能的重要手段。本项目采用体外血管/神经细胞模型和体内血管/神经特异性基因敲除小鼠模型，利用先进的同步辐射三维成像技术、染色质免疫共沉淀、甲基化测序和荧光素酶实验等技术，从分子、细胞和整体水平揭示了表观遗传因子UTX与microRNA通过形成表观修饰网络，参与神经血管可塑性调控，阐明了其在SCI中对神经血管再生的作用机理，为促进脊髓神经功能恢复，治疗SCI提供实验基础和理论依据。