Upregulation of EMMPRIN (OX47) in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury.
Upregulation of EMMPRIN (OX47) in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury.
复制标题
大鼠背根神经节 EMMPRIN (OX47) 的上调导致神经损伤后机械性异常性疼痛的发生
DOI：
10.1155/2015/249756
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发表时间：
2015
影响因子：
3.1
通讯作者：
Lu Y
中科院分区：
文献类型：
--
作者：
Wang Q;Sun Y;Ren Y;Gao Y;Tian L;Liu Y;Pu Y;Gou X;Chen Y;Lu Y
基质金属蛋白酶（MMP）广泛参与与各种神经退行性疾病相关的炎症和组织重塑，并在伤害感受和异常性疼痛中发挥重要作用。细胞外基质金属蛋白酶诱导物 (EMMPRIN) 在 MMP 活性中发挥着关键的调节作用。然而，EMMPRIN 在神经性疼痛发生中的作用尚不清楚。采用Western blotting、实时定量RT-PCR（qRT-PCR）和免疫荧光法测定神经损伤后大鼠背根神经节（DRG）中EMMPRIN/OX47信使RNA和蛋白的变化及其细胞定位。通过缩爪阈值测试来评估脊神经结扎（SNL）模型中的疼痛行为。在 SNL 前一天将含有 OX47 shRNA 的慢病毒注射到 DRG 中。 SNL后同侧DRG中OX47 mRNA和蛋白的表达水平均显着上调。 OX47主要表达于DRG的细胞外基质中。体内施用针对 OX47 的 shRNA 显着减轻了 SNL 诱导的机械异常性疼痛。总之，周围神经损伤导致DRG细胞外基质中OX47的上调。针对 OX47 的 RNA 干扰显着抑制 OX47 mRNA 的表达和机械异常性疼痛的发生。 OX47 表达的改变可能导致神经损伤后神经性疼痛的发生。
Matrix metalloproteinases (MMPs) are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG) after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL) model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.