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粒细胞集落刺激因子(GCSF)通过上调背根神经节中早期 microRNA-122 的表达,抑制单核细胞趋化蛋白-1(MCP-1)的表达,从而减轻神经病理性疼痛。

Granulocyte Colony Stimulating Factor (GCSF) Can Attenuate Neuropathic Pain by Suppressing Monocyte Chemoattractant Protein-1 (MCP-1) Expression, through Upregulating the Early MicroRNA-122 Expression in the Dorsal Root Ganglia.

机构信息

Department of Life Science, National Taiwan Normal University, Taipei 11677, Taiwan.

Department of Neurology, Chang Gung Memorial Hospital-Linkou Medical Center and Chang Gung University College of Medicine, Taipei 33305, Taiwan.

出版信息

Cells. 2020 Jul 11;9(7):1669. doi: 10.3390/cells9071669.

DOI:10.3390/cells9071669
PMID:32664488
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7408430/
Abstract

Our previous animal studies and several human clinical trials have shown that granulocyte-colony stimulating factor (GCSF) can attenuate neuropathic pain through various mechanisms. GCSF itself is also a multipotent cytokine that can modulate microribonucleic acid (microRNA) expression profiles in vitro. In this study, we used the NanoString nCounter analysis system to screen the expression of different rodent microRNAs at early stage after nerve injury and studied the expression of related cytokines/chemokines in the dorsal root ganglia (DRGs) of rats that underwent chronic constriction injury (CCI) to explore the underlying mechanisms of the analgesic effects of GCSF. We found that microRNA-122 expression was downregulated by CCI; in contrast, GCSF treatment significantly upregulated microRNA-122 expression in the DRGs of CCI rats on the 1st day after nerve injury. We further studied the expression of different cytokines/chemokines (IL-1β, IL-6, and monocyte chemoattractant protein-1 (MCP-1)) that were modulated by microRNA-122. MCP-1 has been reported to participate in neuropathic pain development, and its expression on the DRGs of vehicle-treated CCI rats was significantly higher than that on the DRGs of sham-operated rats; in contrast, GCSF-treated rats exhibited significantly lower MCP-1 expression in the DRG than vehicle-treated rats on the 7th day after nerve injury. An early GCSF treatment can suppress MCP-1 expressions, through upregulating microRNA-122 expressions in the DRGs of CCI rats at an earlier stage, thus indirectly attenuating neuropathic pain development.

摘要

我们之前的动物研究和几项人类临床试验表明,粒细胞集落刺激因子(GCSF)可以通过多种机制减轻神经性疼痛。GCSF 本身也是一种多能细胞因子,能够在体外调节微小核糖核酸(microRNA)表达谱。在这项研究中,我们使用 NanoString nCounter 分析系统筛选了神经损伤后早期不同啮齿类动物 microRNA 的表达情况,并研究了慢性缩窄性损伤(CCI)大鼠背根神经节(DRG)中相关细胞因子/趋化因子的表达情况,以探讨 GCSF 镇痛作用的潜在机制。我们发现,CCI 可下调 microRNA-122 的表达;相反,CCI 大鼠神经损伤后第 1 天,GCSF 治疗可显著上调 DRG 中 microRNA-122 的表达。我们进一步研究了受 microRNA-122 调节的不同细胞因子/趋化因子(IL-1β、IL-6 和单核细胞趋化蛋白-1(MCP-1))的表达情况。MCP-1 已被报道参与神经性疼痛的发展,其在 vehicle 处理的 CCI 大鼠 DRG 中的表达明显高于 sham 手术大鼠;相反,GCSF 处理的大鼠在神经损伤后第 7 天,DRG 中 MCP-1 的表达明显低于 vehicle 处理的大鼠。早期 GCSF 治疗可以通过在 CCI 大鼠的 DRG 中更早地上调 microRNA-122 的表达,从而抑制 MCP-1 的表达,从而间接减轻神经性疼痛的发展。

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