背景:轴突导向因子可能在α-突触核蛋白相关神经退行性疾病中发挥重要作用。目的:探讨轴突导向因子在α-突触核蛋白相关神经退行性疾病中的作用及机制。方法:由第一作者系统检索中国知网、万方数据库、PubMed、Nature、Embase、Web of S...背景:轴突导向因子可能在α-突触核蛋白相关神经退行性疾病中发挥重要作用。目的:探讨轴突导向因子在α-突触核蛋白相关神经退行性疾病中的作用及机制。方法:由第一作者系统检索中国知网、万方数据库、PubMed、Nature、Embase、Web of Sciense、JAMA、BMJ等数据库,中文检索词为“帕金森病,轴突导向因子,路易体痴呆,多系统衰竭,单纯性自主神经功能衰竭”,英文检索词为“Parkinson’s disease,axon guidance molecules,Netrin,Ephrin,Semaphorin,Slit,Dementia with Lewy Bodies,Multiple System Atrophy,Pure Autonomic Failure”,全面收集并整理近年来有关轴突导向因子与α-突触核蛋白相关神经退行性疾病的文献,最终纳入89篇文献进行综述分析。结果与结论:轴突导向因子蛋白家族包括Netrins、Ephrins、Semaphorins和Slits。Netrins通过影响肠道因子、依赖DCC受体调节多巴胺能神经元活力,进而影响神经退行性疾病进程。在Ephrins家族中,EphrinA/EphA参与介导神经元再生信号,EphA1借CXC趋化因子配体12/CXC趋化因子受体4通路调节炎症与神经病理,影响疾病发展。Semaphorins家族中的Semaphorins-3通过引导多巴胺能神经元轴突从黑质向纹状体生长,进而改善神经退行性疾病的行为学症状。在多巴胺能神经元轴突传导通路上,Slits经Slit/Robo等信号协作调控轴突定位与寻路过程,确保神经元信号传导路径的准确性,对神经元连接的维持与修复具有重要意义。展开更多
[目的]研究Netrin1调控ELF3对子宫内膜癌HEC-1B细胞转移活性的影响。[方法]将36份组织样本分为2组:子宫内膜癌组、癌旁组,每组18份。蛋白免疫印迹检测癌组织和癌旁组织中Netrin1与ELF3的表达。将子宫内膜癌HEC-1B细胞设置为3组:siRNA N...[目的]研究Netrin1调控ELF3对子宫内膜癌HEC-1B细胞转移活性的影响。[方法]将36份组织样本分为2组:子宫内膜癌组、癌旁组,每组18份。蛋白免疫印迹检测癌组织和癌旁组织中Netrin1与ELF3的表达。将子宫内膜癌HEC-1B细胞设置为3组:siRNA NC组、siRNA Netrin1组和siRNA ELF3组。MTT实验法检测HEC-1B细胞的增殖能力,细胞划痕实验方法分析HEC-1B细胞的迁移能力,TUNEL实验检测HEC-1B细胞的凋亡率,蛋白免疫印迹方法分析HEC-1B细胞中Netrin1与ELF3蛋白的表达。[结果]与癌旁组织比较,子宫内膜癌组织Netrin1与ELF3的表达上调(0.19±0.06 vs 0.73±0.02,P<0.05;0.23±0.03 vs 0.69±0.08,P<0.05)。与siRNA NC组比较,siRNA Netrin1以及siRNA ELF3组的子宫内膜癌HEC-1B细胞增殖能力下降;siRNA Netrin1以及siRNA ELF3组的HEC-1B细胞迁移能力下降;siRNA Netrin1以及siRNA ELF3组的HEC-1B细胞凋亡率增加(1.15%±0.08%vs 10.31%±0.06%vs 9.96%±0.17%,P<0.05);siRNA Netrin1组的HEC-1B细胞Netrin1、ELF3表达降低(0.78±0.06 vs 0.31±0.07 vs 0.75±0.11,P<0.05;0.73±0.08 vs 0.25±0.03 vs 0.29±0.07,P<0.05);siRNA ELF3组的HEC-1B细胞ELF3表达降低。[结论]子宫内膜癌组织中Netrin1与ELF3的表达水平增加。抑制Netrin1表达后,子宫内膜癌HEC-1B细胞的增殖与迁移能力减弱,凋亡率增加,Netrin1对子宫内膜癌的作用与调控ELF3相关。展开更多
The peripheral nervous system has an astonishing ability to regenerate following a compression or crush injury;however,the potential for full repair following a transection injury is much less.Currently,the major clin...The peripheral nervous system has an astonishing ability to regenerate following a compression or crush injury;however,the potential for full repair following a transection injury is much less.Currently,the major clinical challenge for peripheral nerve repair come from long gaps between the proximal and distal nerve stumps,which prevent regenerating axons reaching the distal nerve.Precise axon targeting during nervous system development is controlled by families of axon guidance molecules including Netrins,Slits,Ephrins and Semaphorins.Several recent studies have indicated key roles of Netrin1,Slit3 and EphrinB2 signalling in controlling the formation of new nerve bridge tissue and precise axon regeneration after peripheral nerve transection injury.Inside the nerve bridge,nerve fibroblasts express EphrinB2 while migrating Schwann cells express the receptor EphB2.EphrinB2/EphB2 signalling between nerve fibroblasts and migrating Schwann cells is required for Sox2 upregulation in Schwann cells and the formation of Schwann cell cords within the nerve bridge to allow directional axon growth to the distal nerve stump.Macrophages in the outermost layer of the nerve bridge express Slit3 while migrating Schwann cells and regenerating axons express the receptor Robo1;within Schwann cells,Robo1 expression is also Sox2-dependent.Slit3/Robo1 signalling is required to keep migrating Schwann cells and regenerating axons inside the nerve bridge.In addition to the Slit3/Robo1 signalling system,migrating Schwann cells also express Netrin1 and regenerating axons express the DCC receptor.It appears that migrating Schwann cells could also use Netrin1 as a guidance cue to direct regenerating axons across the peripheral nerve gap.Engineered neural tissues have been suggested as promising alternatives for the repair of large peripheral nerve gaps.Therefore,understanding the function of classic axon guidance molecules in nerve bridge formation and their roles in axon regeneration could be highly beneficial in developing engineered neural tissue for more effective peripheral nerve repair.展开更多
文摘背景:轴突导向因子可能在α-突触核蛋白相关神经退行性疾病中发挥重要作用。目的:探讨轴突导向因子在α-突触核蛋白相关神经退行性疾病中的作用及机制。方法:由第一作者系统检索中国知网、万方数据库、PubMed、Nature、Embase、Web of Sciense、JAMA、BMJ等数据库,中文检索词为“帕金森病,轴突导向因子,路易体痴呆,多系统衰竭,单纯性自主神经功能衰竭”,英文检索词为“Parkinson’s disease,axon guidance molecules,Netrin,Ephrin,Semaphorin,Slit,Dementia with Lewy Bodies,Multiple System Atrophy,Pure Autonomic Failure”,全面收集并整理近年来有关轴突导向因子与α-突触核蛋白相关神经退行性疾病的文献,最终纳入89篇文献进行综述分析。结果与结论:轴突导向因子蛋白家族包括Netrins、Ephrins、Semaphorins和Slits。Netrins通过影响肠道因子、依赖DCC受体调节多巴胺能神经元活力,进而影响神经退行性疾病进程。在Ephrins家族中,EphrinA/EphA参与介导神经元再生信号,EphA1借CXC趋化因子配体12/CXC趋化因子受体4通路调节炎症与神经病理,影响疾病发展。Semaphorins家族中的Semaphorins-3通过引导多巴胺能神经元轴突从黑质向纹状体生长,进而改善神经退行性疾病的行为学症状。在多巴胺能神经元轴突传导通路上,Slits经Slit/Robo等信号协作调控轴突定位与寻路过程,确保神经元信号传导路径的准确性,对神经元连接的维持与修复具有重要意义。
文摘[目的]研究Netrin1调控ELF3对子宫内膜癌HEC-1B细胞转移活性的影响。[方法]将36份组织样本分为2组:子宫内膜癌组、癌旁组,每组18份。蛋白免疫印迹检测癌组织和癌旁组织中Netrin1与ELF3的表达。将子宫内膜癌HEC-1B细胞设置为3组:siRNA NC组、siRNA Netrin1组和siRNA ELF3组。MTT实验法检测HEC-1B细胞的增殖能力,细胞划痕实验方法分析HEC-1B细胞的迁移能力,TUNEL实验检测HEC-1B细胞的凋亡率,蛋白免疫印迹方法分析HEC-1B细胞中Netrin1与ELF3蛋白的表达。[结果]与癌旁组织比较,子宫内膜癌组织Netrin1与ELF3的表达上调(0.19±0.06 vs 0.73±0.02,P<0.05;0.23±0.03 vs 0.69±0.08,P<0.05)。与siRNA NC组比较,siRNA Netrin1以及siRNA ELF3组的子宫内膜癌HEC-1B细胞增殖能力下降;siRNA Netrin1以及siRNA ELF3组的HEC-1B细胞迁移能力下降;siRNA Netrin1以及siRNA ELF3组的HEC-1B细胞凋亡率增加(1.15%±0.08%vs 10.31%±0.06%vs 9.96%±0.17%,P<0.05);siRNA Netrin1组的HEC-1B细胞Netrin1、ELF3表达降低(0.78±0.06 vs 0.31±0.07 vs 0.75±0.11,P<0.05;0.73±0.08 vs 0.25±0.03 vs 0.29±0.07,P<0.05);siRNA ELF3组的HEC-1B细胞ELF3表达降低。[结论]子宫内膜癌组织中Netrin1与ELF3的表达水平增加。抑制Netrin1表达后,子宫内膜癌HEC-1B细胞的增殖与迁移能力减弱,凋亡率增加,Netrin1对子宫内膜癌的作用与调控ELF3相关。
文摘The peripheral nervous system has an astonishing ability to regenerate following a compression or crush injury;however,the potential for full repair following a transection injury is much less.Currently,the major clinical challenge for peripheral nerve repair come from long gaps between the proximal and distal nerve stumps,which prevent regenerating axons reaching the distal nerve.Precise axon targeting during nervous system development is controlled by families of axon guidance molecules including Netrins,Slits,Ephrins and Semaphorins.Several recent studies have indicated key roles of Netrin1,Slit3 and EphrinB2 signalling in controlling the formation of new nerve bridge tissue and precise axon regeneration after peripheral nerve transection injury.Inside the nerve bridge,nerve fibroblasts express EphrinB2 while migrating Schwann cells express the receptor EphB2.EphrinB2/EphB2 signalling between nerve fibroblasts and migrating Schwann cells is required for Sox2 upregulation in Schwann cells and the formation of Schwann cell cords within the nerve bridge to allow directional axon growth to the distal nerve stump.Macrophages in the outermost layer of the nerve bridge express Slit3 while migrating Schwann cells and regenerating axons express the receptor Robo1;within Schwann cells,Robo1 expression is also Sox2-dependent.Slit3/Robo1 signalling is required to keep migrating Schwann cells and regenerating axons inside the nerve bridge.In addition to the Slit3/Robo1 signalling system,migrating Schwann cells also express Netrin1 and regenerating axons express the DCC receptor.It appears that migrating Schwann cells could also use Netrin1 as a guidance cue to direct regenerating axons across the peripheral nerve gap.Engineered neural tissues have been suggested as promising alternatives for the repair of large peripheral nerve gaps.Therefore,understanding the function of classic axon guidance molecules in nerve bridge formation and their roles in axon regeneration could be highly beneficial in developing engineered neural tissue for more effective peripheral nerve repair.
