树脂毒素诱导的神经性疼痛大鼠脊髓中的长链非编码RNA和mRNA图谱
Long Non-Coding RNA and mRNA Profiles in the Spinal Cord of Rats with Resiniferatoxin-Induced Neuropathic Pain.
作者信息
Wu Caihua, Liu Yongmin, Wan Kexing, Lan Yuye, Jia Min, Lin Lixue, Gao Shan, Chen Ke, Yang Jinmei, Pan Hui-Lin, Li Man, Mao Hongrong
机构信息
Department of Acupuncture, Wuhan First Hospital, Wuhan, Hubei Province, 430030, People's Republic of China.
Department of Neurobiology, School of Basic medicine, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei Province, 430030, People's Republic of China.
出版信息
J Pain Res. 2022 Jul 30;15:2149-2160. doi: 10.2147/JPR.S368599. eCollection 2022.
PURPOSE
The ultrapotent transient receptor potential vanilloid 1 (TRPV1) agonist resiniferatoxin (RTX) induces small-fiber sensory neuropathy, which has been widely used model of postherpetic neuralgia to study mechanisms of neuropathic pain and new analgesics. The long non-coding RNA (lncRNA) and mRNA expression profiles in spinal dorsal horn tissues of rats six weeks after RTX injection to identify new RNAs related to neuropathic pain.
METHODS
Microarray technology was applied to determine lncRNA expressions in spinal dorsal horn samples of adult rats 6 weeks after treatment with RTX or vehicle. The lncNA/mRNA co-expression network was constructed, and differential expression patterns of lncRNA and mRNA in RTX-treated rats were identified. Differential expressions of lncRNAs and mRNAs between RTX-treated samples and control samples were examined by RT-qPCR.
RESULTS
Microarray analyses showed that 745 mRNA and 139 lncRNAs were upregulated, whereas 590 mRNA and 140 lncRNAs were downregulated in spinal dorsal horn tissues after RTX exposure. TargetScan was used to predict mRNA targets for these lncRNAs, which showed that the transcripts with multiple predicted target sites were related to neurologically important pathways. In addition, differential expressions of lncRNA (ENSRNOG00000022535, ENSRNOG00000042027, NR_027478, NR_030675) and Apobec3b mRNA in spinal cord tissue samples were validated, which confirmed the microarray data. The association between NR_030675 and Apobec3b levels was confirmed, which may be related to neuropathic pain.
CONCLUSION
Our study reveals lncRNA and mRNA of molecule targets that are enriched in the spinal cord dorsal horn and provides new information for further investigation on the mechanisms and therapeutics of neuropathic pain.
目的
超高效瞬时受体电位香草酸受体1（TRPV1）激动剂树脂毒素（RTX）可诱发小纤维感觉神经病变，该病变已成为广泛用于研究神经性疼痛机制和新型镇痛药的带状疱疹后神经痛模型。通过检测RTX注射六周后大鼠脊髓背角组织中的长链非编码RNA（lncRNA）和mRNA表达谱，以鉴定与神经性疼痛相关的新RNA。
方法
应用微阵列技术测定成年大鼠在接受RTX或赋形剂治疗6周后脊髓背角样本中的lncRNA表达。构建lncNA/mRNA共表达网络，并鉴定RTX处理大鼠中lncRNA和mRNA的差异表达模式。通过RT-qPCR检测RTX处理样本与对照样本之间lncRNA和mRNA的差异表达。
结果
微阵列分析显示，RTX暴露后脊髓背角组织中745种mRNA和139种lncRNA上调，而590种mRNA和140种lncRNA下调。使用TargetScan预测这些lncRNA的mRNA靶标，结果表明具有多个预测靶位点的转录本与神经重要通路相关。此外，还验证了脊髓组织样本中lncRNA（ENSRNOG00000022535、ENSRNOG00000042027、NR_027478、NR_030675）和载脂蛋白B mRNA的差异表达，这证实了微阵列数据。证实了NR_030675与载脂蛋白B水平之间的关联，这可能与神经性疼痛有关。
结论
我们的研究揭示了脊髓背角中富集的分子靶标的lncRNA和mRNA，并为进一步研究神经性疼痛的机制和治疗方法提供了新信息。
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