miR-223-3p 通过靶向 MKNK2 和 MAPK/ERK 信号通路缓解雄性小鼠三叉神经病理性疼痛。
MiR-223-3p alleviates trigeminal neuropathic pain in the male mouse by targeting MKNK2 and MAPK/ERK signaling.
机构信息
Department of Neurology, The Affiliated Hospital of Putian University, Putian, China.
Department of Stomatology, The First Hospital of Putian City, Putian, China.
出版信息
Brain Behav. 2022 Jul;12(7):e2634. doi: 10.1002/brb3.2634. Epub 2022 May 24.
BACKGROUND
Trigeminal neuralgia (TN) is a neuropathic pain that occurs in branches of the trigeminal nerve. MicroRNAs (miRNAs) have been considered key mediators of neuropathic pain. This study was aimed to elucidate the pathophysiological function and mechanisms of miR-223-3p in mouse models of TN.
METHODS
Infraorbital nerve chronic constriction injury (CCI-ION) was applied in male C57BL/6J mice to establish mouse models of TN. Pain responses were assessed utilizing Von Frey method. The expression of miR-223-3p, MKNK2, and MAPK/ERK pathway protein in trigeminal ganglions (TGs) of CCI-ION mice was measured using RT-qPCR and Western blotting. The concentrations of inflammatory cytokines were evaluated using Western blotting. The relationship between miR-223-3p and MKNK2 was tested by a luciferase reporter assay.
RESULTS
We found that miR-223-3p was downregulated, while MKNK2 was upregulated in TGs of CCI-ION mice. MiR-223-3p overexpression by an intracerebroventricular injection of Lv-miR-223-3p attenuated trigeminal neuropathic pain in CCI-ION mice, as well as reduced the protein levels of pro-inflammatory cytokines in TGs of CCI-ION mice. MKNK2 was verified to be targeted by miR-223-3p. Additionally, miR-223-3p overexpression decreased the phosphorylation levels of ERK1/2, JNK, and p38 protein in TGs of CCI-ION mice to inhibit MAPK/ERK signaling.
CONCLUSIONS
Overall, miR-223-3p attenuates the development of TN by targeting MKNK2 to suppress MAPK/ERK signaling.
背景
三叉神经痛（TN）是一种发生在三叉神经分支的神经性疼痛。MicroRNAs（miRNAs）被认为是神经性疼痛的关键介质。本研究旨在阐明 miR-223-3p 在 TN 小鼠模型中的病理生理功能和机制。
方法
采用眶下神经慢性缩窄性损伤（CCI-ION）建立雄性 C57BL/6J 小鼠 TN 模型。采用 Von Frey 法评估疼痛反应。采用 RT-qPCR 和 Western blot 法检测三叉神经节（TGs）中 miR-223-3p、MKNK2 和 MAPK/ERK 通路蛋白的表达。采用 Western blot 法评估炎性细胞因子的浓度。通过荧光素酶报告实验检测 miR-223-3p 和 MKNK2 之间的关系。
结果
我们发现，CCI-ION 小鼠 TGs 中 miR-223-3p 下调，而 MKNK2 上调。通过脑室内注射 Lv-miR-223-3p 过表达 miR-223-3p 可减轻 CCI-ION 小鼠的三叉神经病理性疼痛，并降低 CCI-ION 小鼠 TGs 中促炎细胞因子的蛋白水平。MKNK2 被证实是 miR-223-3p 的靶标。此外，miR-223-3p 过表达可降低 CCI-ION 小鼠 TGs 中 ERK1/2、JNK 和 p38 蛋白的磷酸化水平，从而抑制 MAPK/ERK 信号通路。
结论
总之，miR-223-3p 通过靶向 MKNK2 抑制 MAPK/ERK 信号通路来减轻 TN 的发展。
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