MiR-30b Attenuates Neuropathic Pain by Regulating Voltage-Gated Sodium Channel Nav1.3 in Rats.
MiR-30b Attenuates Neuropathic Pain by Regulating Voltage-Gated Sodium Channel Nav1.3 in Rats.
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MiR-30b 通过调节大鼠电压门控钠通道 Nav1.3 减轻神经性疼痛
DOI：
10.3389/fnmol.2017.00126
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发表时间：
2017
影响因子：
4.8
通讯作者：
Zang W
中科院分区：
文献类型：
--
作者：
Su S;Shao J;Zhao Q;Ren X;Cai W;Li L;Bai Q;Chen X;Xu B;Wang J;Cao J;Zang W
Nav1.3是电压门控钠通道中的河豚毒素敏感异构体，与神经性疼痛密切相关。它可以在神经损伤后上调，但其生物学功能尚不清楚。MicroRNAs （miRNAs）是一种内源性非编码rna，可以通过与靶mrna结合来调节转录后基因的表达。利用Target Scan软件，我们发现SCN3A是miR-30b的主要靶点，然后我们确定miR-30b是通过TNF-α刺激转染miR-30b agomir还是通过转染miR-30b antagomir在初级背根神经节（DRG）神经元中调控Nav1.3的表达。采用脊髓神经结扎（SNL）模型确定miR-30b对神经性疼痛的贡献，评估Nav1.3 mRNA和蛋白表达的变化，了解大鼠对机械和热刺激的敏感性。我们的研究结果显示，转染miR-30b agomir可下调原代DRG神经元中TNF-α刺激的Nav1.3 mRNA。此外，miR-30b过表达可显著减轻SNL引起的神经性疼痛，DRG神经元和脊髓中Nav1.3 mRNA和蛋白的表达均降低。发现miR-30b拮抗剂引起Nav1.3的激活。这些数据提示miR-30b可能通过调节Nav1.3的表达参与神经性疼痛的发生发展，可能成为神经性疼痛的新治疗靶点。观点：本研究首次探讨了miR-30b和Nav1.3在脊神经结扎引起的神经性疼痛中的重要作用，我们的证据可能为改善疼痛的治疗方法提供新的见解。
Nav1.3 is a tetrodotoxin-sensitive isoform among voltage-gated sodium channels that are closely associated with neuropathic pain. It can be up-regulated following nerve injury, but its biological function remains uncertain. MicroRNAs (miRNAs) are endogenous non-coding RNAs that can regulate post-transcriptional gene expression by binding with their target mRNAs. Using Target Scan software, we discovered that SCN3A is the major target of miR-30b, and we then determined whether miR-30b regulated the expression of Nav1.3 by transfecting miR-30b agomir through the stimulation of TNF-α or by transfecting miR-30b antagomir in primary dorsal root ganglion (DRG) neurons. The spinal nerve ligation (SNL) model was used to determine the contribution of miR-30b to neuropathic pain, to evaluate changes in Nav1.3 mRNA and protein expression, and to understand the sensitivity of rats to mechanical and thermal stimuli. Our results showed that miR-30b agomir transfection down-regulated Nav1.3 mRNA stimulated with TNF-α in primary DRG neurons. Moreover, miR-30b overexpression significantly attenuated neuropathic pain induced by SNL, with decreases in the expression of Nav1.3 mRNA and protein both in DRG neurons and spinal cord. Activation of Nav1.3 caused by miR-30b antagomir was identified. These data suggest that miR-30b is involved in the development of neuropathic pain, probably by regulating the expression of Nav1.3, and might be a novel therapeutic target for neuropathic pain. Perspective: This study is the first to explore the important role of miR-30b and Nav1.3 in spinal nerve ligation-induced neuropathic pain, and our evidence may provide new insight for improving therapeutic approaches to pain.