MiR-200a-3p Attenuates Neuropathic Pain by Suppressing the Bromodomain-Containing Protein 3-Nuclear Factor-κB Pathway

IF 3.2 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Biochemical and Molecular Toxicology Pub Date : 2024-12-09 DOI:10.1002/jbt.70041

Chao Deng, Xuequan Yuan, Xuezheng Lin, Sitong Liu

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引用次数: 0

Abstract

MicroRNAs (miRNAs) have key roles in the pathological processes of neuropathic pain. Here, our aim was to elucidate the function of miR-200a-3p as well as its related regulatory mechanism in neuropathic pain. An animal model of neuropathic pain was established by chronic constriction injury (CCI) induction. The knockdown experiments are performed by injecting a lentiviral construct intrathecally. MiR-200a-3p and bromodomain-containing protein 3 (BRD3) expression in rat spinal cord was determined using RT-qPCR. The mechanical, thermal, and cold responses in animals were assessed at the indicated time after surgery. The levels of inflammatory cytokines in rat spinal cord were measured by ELISA. The changes in NF-κB signaling-related molecules in rat spinal cord were determined using western blot and immunofluorescence. MiR-200a-3p was underexpressed in CCI rats in a time-dependent manner. Overexpression of miR-200a-3p decreased mechanical hyperalgesia and thermal sensitivity to attenuate neuropathic pain in rats. BRD3 was targeted by miR-200a-3p. Additionally, downregulation of BRD3 inhibited neuropathic pain progression. Moreover, overexpression of BRD3 rescued the effect of miR-200a-3p on NF-κB signaling and neuropathic pain in CCI rats. MiR-200a-3p attenuates neuropathic pain via downregulating BRD3 to block NF-κB signaling.

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微RNA（miRNA）在神经病理性疼痛的病理过程中起着关键作用。本文旨在阐明 miR-200a-3p 在神经病理性疼痛中的功能及其相关调控机制。我们通过慢性收缩性损伤（CCI）诱导建立了神经病理性疼痛动物模型。通过鞘内注射慢病毒构建体进行基因敲除实验。采用 RT-qPCR 方法测定了大鼠脊髓中 MiR-200a-3p 和含溴域蛋白 3（BRD3）的表达。在手术后的指定时间评估动物的机械、热和冷反应。用酶联免疫吸附法测定大鼠脊髓中炎性细胞因子的水平。大鼠脊髓中与 NF-κB 信号相关分子的变化采用 Western 印迹和免疫荧光法进行测定。CCI大鼠体内的miR-200a-3p呈时间依赖性低表达。过表达 miR-200a-3p 可降低大鼠的机械痛和热敏感性，从而减轻神经病理性疼痛。miR-200a-3p 靶向了 BRD3。此外，下调 BRD3 可抑制神经病理性疼痛的发展。此外，过量表达 BRD3 可以缓解 miR-200a-3p 对 CCI 大鼠 NF-κB 信号转导和神经病理性疼痛的影响。MiR-200a-3p 通过下调 BRD3 来阻断 NF-κB 信号传导，从而减轻神经病理性疼痛。

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来源期刊

Journal of Biochemical and Molecular Toxicology 生物-毒理学

CiteScore

5.80

自引率

2.80%

发文量

277

审稿时长

6-12 weeks

期刊介绍： The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.