miR‐124‐3p attenuates neuropathic pain induced by chronic sciatic nerve injury in rats via targeting EZH2
miR‐124‐3p attenuates neuropathic pain induced by chronic sciatic nerve injury in rats via targeting EZH2
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DOI：
10.1002/jcb.27861
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发表时间：
2018-11
影响因子：
4
通讯作者：
Yang Zhang;Hai-Lin Liu;Li-jun An;Lin Li;Meng Wei;D. Ge;Z. Su
中科院分区：
文献类型：
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作者：
Yang Zhang;Hai-Lin Liu;Li-jun An;Lin Li;Meng Wei;D. Ge;Z. Su
新出现的证据表明，microrna在神经性疼痛的发展中起着关键作用。然而，mirna在调节神经性疼痛中的生物学作用仍然知之甚少。在我们目前的研究中，我们发现miR‐124‐3p在慢性坐骨神经损伤（CCI）后的大鼠中显著下调。此外，miR‐124‐3p的过表达明显抑制机械异常性痛和热痛觉过敏。同时，据报道，神经炎症对神经性疼痛的进展有很大的促进作用。在这里，我们发现炎症细胞因子（IL‐6，IL‐1β和TNF‐）蛋白在CCI后的大鼠中的表达大大增加，miR‐124‐3p模拟抑制炎症细胞因子水平。miR‐124‐3p同样可以减轻脂多糖培养的脊髓小胶质细胞的炎症产生。生物信息学分析显示EZH2作为miR‐124‐3p的直接靶点，参与miR‐124‐3p对神经性疼痛发展和神经炎症的调节作用。我们观察到miR - 124 - 3p能够通过靶向EZH2促进神经炎症和神经性疼痛。它们之间的直接相关性在我们当前的研究中通过双荧光素酶报告分析得到了验证。随后，研究表明EZH2可以消除miR - 124 - 3p对CCI大鼠神经性疼痛进展的抑制作用。综上所述，我们的研究结果强调了miR - 124 - 3p对神经性疼痛的新贡献，并指出了开发神经性疼痛新治疗方案的可能性。
Emerging evidence has suggested that microRNAs play a critical role in neuropathic pain development. However, the biological role of miRNAs in regulating neuropathic pain remains barely known. In our present study, we found that miR‐124‐3p was significantly downregulated in rats after chronic sciatic nerve injury (CCI). In addition, it was showed that overexpression of miR‐124‐3p obviously repressed mechanical allodynia and heat hyperalgesia. Meanwhile, it has been reported that neuroinflammation can contribute a lot to neuropathic pain progression. Here, we found that inflammatory cytokine (IL‐6, IL‐1β, and TNF‐⍺) protein expression in rats after CCI greatly increased and miR‐124‐3p mimics depressed inflammation cytokine levels. Consistently, miR‐124‐3p alleviated inflammation production in lipopolysaccharide‐incubated spinal microglial cells. Bioinformatics analysis revealed that EZH2 acted as a direct target of miR‐124‐3p, which participated in the miR‐124‐3p‐modulated effects on neuropathic pain development and neuroinflammation. We observed that miR‐124‐3p was able to promote neuroinflammation and neuropathic pain through targeting EZH2. The direct correlation between them was validated in our current study using dual‐luciferase reporter assays. Subsequently, it was manifested that EZH2 abrogated the inhibitory role of miR‐124‐3p on neuropathic pain progression in CCI rats. Taken these together, our findings highlighted a novel contribution of miR‐124‐3p to neuropathic pain and indicated the possibilities for developing novel therapeutic options for neuropathic pain.