Role of plasminogen activator in spinal cord remodeling after spinal cord injury.

Role of plasminogen activator in spinal cord remodeling after spinal cord injury.
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DOI:
10.1016/j.resp.2009.07.021
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发表时间:
2009-11-30
影响因子:
2.3
通讯作者:
Minor, Kenneth
Minor, Kenneth
中科院分区:
医学4区
文献类型:
--
作者:
Seeds, Nicholas W.;Akison, Lisa;Minor, Kenneth

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纤溶酶原激活物在脊髓损伤后与交叉膈现象(CPP)相关的突触可塑性和呼吸功能的恢复中起积极作用。遗传学方法已经被用来确定这种突触可塑性的分子机制。缺乏纤溶酶原激活物/纤溶酶系统不同基因的基因敲除小鼠表明,在C2半切后1-2小时的关键延迟期内,需要表达尿激酶型纤溶酶原激活剂(UPA)才能获得良好的CPP反应。UPA基因敲除小鼠未能显示构成CPP反应基础的膈运动神经元突触的结构重塑。UPA促进膈运动神经元突触可塑性的潜在机制已经被探索。同侧膈神经运动核(PMN)中uPA受体uPAR和LRP-1的表达在C2-半切后均上调。基因芯片数据的比较和实时定量聚合酶链式反应分析表明,uPA与PMN中这些细胞表面受体相互作用的下游可能存在细胞信号通路。对这些uPA介导的信号通路的了解可能会确定药物激活突触可塑性的潜在方法,这些突触可塑性是恢复膈运动神经元活性所必需的。
Plasminogen activators play an active role in synaptic plasticity associated with the crossed phrenic phenomenon (CPP) and recovery of respiratory function following spinal cord injury. A genetic approach has been used to identify molecular mechanisms underlying this synaptic plasticity. Knockout mice lacking different genes in the plasminogen activator/plasmin system demonstrate that expression of urokinase plasminogen activator (uPA) is required during the critical 1-2h delay period following C2-hemisection for acquisition of a good CPP response. uPA knockout mice fail to show the structural remodeling of phrenic motor neuron synapses that underlie the CPP response. Potential mechanisms by which uPA may promote phrenic motor neuron synaptic plasticity have been explored. Expression of uPA receptors, uPAR and LRP-1, are both up-regulated in the ipsilateral phrenic motor nucleus (PMN) following C2-hemisection. A comparison of microarray data and real-time PCR analysis of mRNAs induced in the PMN after hemisection indicate potential cell signaling pathways downstream of uPA’s interaction with these cell surface receptors in the PMN. Knowledge of these uPA-mediated signaling pathways may identify potential means for pharmacological activation of the synaptic plasticity required for recovery of phrenic motor neuron activity.
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