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首页> 外文期刊>BMC Neuroscience >Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after peripheral nerve injury
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Reciprocal regulation of nuclear factor kappa B and its inhibitor ZAS3 after peripheral nerve injury

机译：周围神经损伤后核因子κB及其抑制剂ZAS3的相互调节

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Background NF-κB binds to the κB motif to regulate transcription of genes involved in growth, immunity and inflammation, and plays a pivotal role in the production of pro-inflammatory cytokines after nerve injuries. The zinc finger protein ZAS3 also binds to the κB or similar motif. In addition to competition for common DNA sites, in vitro experiments have shown that ZAS3 can inhibit NF-κB via the association with TRAF2 to inhibit the nuclear translocation of NF-κB. However, the physiological significance of the ZAS3-mediated inhibition of NF-κB has not been demonstrated. The purpose of this study is to characterize ZAS3 proteins in nervous tissues and to use spinal nerve ligation, a neuropathic pain model, to demonstrate a functional relationship between ZAS3 and NF-κB. Results Immunohistochemical experiments show that ZAS3 is expressed in specific regions of the central and peripheral nervous system. Abundant ZAS3 expression is found in the trigeminal ganglion, hippocampal formation, dorsal root ganglia, and motoneurons. Low levels of ZAS3 expressions are also found in the cerebral cortex and in the grey matter of the spinal cord. In those nervous tissues, ZAS3 is expressed mainly in the cell bodies of neurons and astrocytes. Together with results of Western blot analyses, the data suggest that ZAS3 protein isoforms with differential cellular distribution are produced in a cell-specific manner. Further, neuropathic pain confirmed by persistent mechanical allodynia was manifested in rats seven days after L5 and L6 lumbar spinal nerve ligation. Changes in gene expression, including a decrease in ZAS3 and an increase in the p65 subunit of NF-κB were observed in dorsal root ganglion ipsilateral to the ligation when compared to the contralateral side. Conclusion ZAS3 is expressed in nervous tissues involved in cognitive function and pain modulation. The down-regulation of ZAS3 after peripheral nerve injury may lead to activation of NF-κB, allowing Wallerian regeneration and induction of NF-κB-dependent gene expression, including pro-inflammatory cytokines. We propose that reciprocal changes in the expression of ZAS3 and NF-κB might generate neuropathic pain after peripheral nerve injury.
机译：背景NF-κB与κB基序结合以调节参与生长，免疫和炎症的基因的转录，并在神经损伤后在促炎性细胞因子的产生中发挥关键作用。锌指蛋白ZAS3也与κB或类似基序结合。除了竞争常见的DNA位点外，体外实验还显示ZAS3可以通过与TRAF2缔合来抑制NF-κB，从而抑制NF-κB的核转运。但是，尚未证明ZAS3介导的NF-κB抑制的生理意义。这项研究的目的是表征神经组织中的ZAS3蛋白，并使用脊髓神经结扎（一种神经性疼痛模型）来证明ZAS3与NF-κB之间的功能关系。结果免疫组织化学实验表明ZAS3在中枢和周围神经系统的特定区域表达。在三叉神经节，海马结构，背根神经节和运动神经元中发现了丰富的ZAS3表达。在大脑皮层和脊髓灰质中也发现低水平的ZAS3表达。在那些神经组织中，ZAS3主要在神经元和星形胶质细胞的细胞体中表达。连同蛋白质印迹分析的结果，数据表明具有差异细胞分布的ZAS3蛋白同工型以细胞特异性方式产生。此外，L5和L6腰椎脊髓神经结扎7天后，大鼠出现了持续性机械异常性疼痛所证实的神经性疼痛。与对侧相比，在同侧结扎的背根神经节中观察到基因表达的变化，包括ZAS3的减少和NF-κB的p65亚基的增加。结论ZAS3在参与认知功能和疼痛调节的神经组织中表达。周围神经损伤后ZAS3的下调可能导致NF-κB活化，从而允许Wallerian再生并诱导NF-κB依赖性基因表达，包括促炎性细胞因子。我们提出ZAS3和NF-κB表达的相互变化可能会在周围神经损伤后产生神经性疼痛。

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