Transcriptome profiling of long noncoding RNAs and mRNAs in spinal cord of a rat model of paclitaxel-induced peripheral neuropathy identifies potential mechanisms mediating neuroinflammation and pain.
Transcriptome profiling of long noncoding RNAs and mRNAs in spinal cord of a rat model of paclitaxel-induced peripheral neuropathy identifies potential mechanisms mediating neuroinflammation and pain.
复制标题
对紫杉醇诱导的周围神经病变大鼠模型脊髓中的长非编码 RNA 和 mRNA 进行转录组分析，确定介导神经炎症和疼痛的潜在机制
DOI：
10.1186/s12974-021-02098-y
复制
发表时间：
2021-02-18
影响因子：
9.3
通讯作者：
Liu B
中科院分区：
文献类型：
--
作者：
Li Y;Yin C;Liu B;Nie H;Wang J;Zeng D;Chen R;He X;Fang J;Du J;Liang Y;Jiang Y;Fang J;Liu B
紫杉醇是一种广泛用于治疗实体瘤的化疗药物。然而，紫杉醇引起的周围神经病变（PIPN）是紫杉醇治疗过程中常见的不良反应，导致患者感觉异常和神经性疼痛。不幸的是，人们对 PIPN 背后的机制仍然知之甚少。长非编码 RNA (lncRNA) 是慢性疼痛治疗的新颖且有前景的靶点，但它们在 PIPN 中的作用仍未被探索。我们通过重复应用紫杉醇建立了大鼠 PIPN 模型。通过免疫染色、RNA 测序 (RNA-Seq) 和生物信息学分析来研究胶质细胞激活并探索 PIPN 模型大鼠脊髓背角 (SCDH) 中的 lncRNA/mRNA 表达谱。 qPCR 和蛋白质测定用于进一步验证。 PIPN模型大鼠后爪出现持久的机械和热痛过敏，并伴有SCDH中星形胶质细胞和小胶质细胞的激活。 RNA-Seq鉴定出PIPN模型大鼠与对照大鼠的SCDH中总共814个差异表达的mRNA（DEmRNA）（包括467个上调和347个下调）和412个DElncRNA（包括145个上调和267个下调）。对DEmRNA和DElncRNA的功能分析发现，最显着富集的通路包括免疫/炎症反应和神经营养素信号通路，它们都是介导神经炎症、中枢敏化和慢性疼痛的重要机制。我们进一步将我们的数据集与其他已发表的神经性疼痛数据集进行比较，并确定了一组广泛参与 PIPN 和其他神经性疼痛病症的免疫反应相关核心基因。最后，对 DElncRNA 和 DEmRNA 进行竞争性 RNA 网络分析，以确定 lncRNA 通过 miRNA 海绵作用对 mRNA 的潜在调控网络。我们的研究提供了 DElncRNA 和 DEmRNA 的转录组分析，并发现免疫和炎症反应是大鼠 PIPN 模型 SCDH 中的主要生物学事件。因此，我们的研究可能有助于识别 PIPN 治疗的有希望的基因或信号通路。在线版本包含可在 10.1186/s12974-021-02098-y 获取的补充材料。
Paclitaxel is a widely prescribed chemotherapy drug for treating solid tumors. However, paclitaxel-induced peripheral neuropathy (PIPN) is a common adverse effect during paclitaxel treatment, which results in sensory abnormalities and neuropathic pain among patients. Unfortunately, the mechanisms underlying PIPN still remain poorly understood. Long noncoding RNAs (lncRNAs) are novel and promising targets for chronic pain treatment, but their involvement in PIPN still remains unexplored. We established a rat PIPN model by repetitive paclitaxel application. Immunostaining, RNA sequencing (RNA-Seq) and bioinformatics analysis were performed to study glia cell activation and explore lncRNA/mRNA expression profiles in spinal cord dorsal horn (SCDH) of PIPN model rats. qPCR and protein assay were used for further validation. PIPN model rats developed long-lasting mechanical and thermal pain hypersensitivities in hind paws, accompanied with astrocyte and microglia activation in SCDH. RNA-Seq identified a total of 814 differentially expressed mRNAs (DEmRNA) (including 467 upregulated and 347 downregulated) and 412 DElncRNAs (including 145 upregulated and 267 downregulated) in SCDH of PIPN model rats vs. control rats. Functional analysis of DEmRNAs and DElncRNAs identified that the most significantly enriched pathways include immune/inflammatory responses and neurotrophin signaling pathways, which are all important mechanisms mediating neuroinflammation, central sensitization, and chronic pain. We further compared our dataset with other published datasets of neuropathic pain and identified a core set of immune response-related genes extensively involved in PIPN and other neuropathic pain conditions. Lastly, a competing RNA network analysis of DElncRNAs and DEmRNAs was performed to identify potential regulatory networks of lncRNAs on mRNA through miRNA sponging. Our study provided the transcriptome profiling of DElncRNAs and DEmRNAs and uncovered immune and inflammatory responses were predominant biological events in SCDH of the rat PIPN model. Thus, our study may help to identify promising genes or signaling pathways for PIPN therapeutics. The online version contains supplementary material available at 10.1186/s12974-021-02098-y.
登录
查看更多内容
复杂区域疼痛综合征 I 型大鼠模型中脊髓背角的表达谱揭示了介导疼痛和神经炎症反应的潜在机制
影响因子：
9.3
作者：
Chen, Ruixiang;Yin, Chengyu;Liu, Boyi
通讯作者：
Liu, Boyi
电针通过抑制脊髓 CXCL12/CXCR4 信号传导减轻 I 型复杂区域疼痛综合征大鼠模型中的机械异常性疼痛
影响因子：
4
作者：
Hu, Qimiao;Zheng, Xiaoli;Liu, Boyi
通讯作者：
Liu, Boyi
影响因子：
14.9
作者：
Franceschini A;Szklarczyk D;Frankild S;Kuhn M;Simonovic M;Roth A;Lin J;Minguez P;Bork P;von Mering C;Jensen LJ
通讯作者：
Jensen LJ
影响因子：
7.4
作者：
Baskozos G;Dawes JM;Austin JS;Antunes-Martins A;McDermott L;Clark AJ;Trendafilova T;Lees JG;McMahon SB;Mogil JS;Orengo C;Bennett DL
通讯作者：
Bennett DL
影响因子：
64.5
作者：
Kopp F;Mendell JT
通讯作者：
Mendell JT