Whole Genomic DNA Methylation Profiling of CpG Sites in Promoter Regions of Dorsal Root Ganglion in Diabetic Neuropathic Pain Mice
Whole Genomic DNA Methylation Profiling of CpG Sites in Promoter Regions of Dorsal Root Ganglion in Diabetic Neuropathic Pain Mice
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糖尿病神经病理性疼痛小鼠背根神经节启动子区 CpG 位点的全基因组 DNA 甲基化分析
DOI：
10.1007/s12031-021-01847-1
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发表时间：
2021-05-05
影响因子：
3.1
通讯作者：
Yang, Fei
中科院分区：
文献类型：
--
作者：
Chen, Wen;Lan, Ting;Yang, Fei
DNA甲基化和去甲基化在神经病理性疼痛中发挥着重要作用。一般来说，启动子区 CpG 位点的 DNA 甲基化会阻碍基因表达，而 DNA 去甲基化则有助于基因表达。在这里，我们评估了糖尿病神经性疼痛 (DNP) 小鼠背根神经节 (DRG) 基因组 DNA 启动子区域 CpG 位点的甲基化状态。在我们的研究中，将链脲佐菌素（STZ）腹腔注射到小鼠体内构建DNP模型。与对照小鼠相比，DNP 小鼠表现出较高的空腹血糖（高于 11.1 mmol/L）、较低的体重和机械性异常性疼痛。全基因组亚硫酸氢盐测序 (WGBS) 揭示了 DNP 小鼠 DRG 中 DNA 启动子区域 CpG 位点的甲基化模式发生了改变。结果显示，376 个启动子区域具有高甲基化 CpG 位点，336 个启动子区域具有低甲基化 CpG 位点。此外，我们的数据表明 DNA 甲基化的改变主要发生在 DNA 启动子区域的 CpG 位点上。京都基因与基因组百科全书 (KEGG) 通路分析显示，差异甲基化 CpG 位点注释的基因参与神经和感觉系统的活动。富集分析表明这些途径中的基因导致糖尿病或疼痛。总之，我们的研究丰富了 DNA 甲基化在 DNP 中的作用。
DNA methylation and demethylation play an important role in neuropathic pain. In general, DNA methylation of CpG sites in the promoter region impedes gene expression, whereas DNA demethylation contributes to gene expression. Here, we evaluated the methylation status of CpG sites in genomic DNA promoter regions in dorsal root ganglions (DRGs) of diabetic neuropathic pain (DNP) mice. In our research, streptozotocin (STZ) was intraperitoneally injected into mice to construct DNP models. The DNP mice showed higher fasting blood glucose (above 11.1 mmol/L), lower body weight, and mechanical allodynia than control mice. Whole-genome bisulfite sequencing (WGBS) revealed an altered methylation pattern in CpG sites in the DNA promoter regions in DRGs of DNP mice. The results showed 376 promoter regions with hypermethylated CpG sites and 336 promoter regions with hypomethylated CpG sites. In addition, our data indicated that altered DNA methylation occurs primarily on CpG sites in DNA promoter regions. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that differentially methylated CpG sites annotated genes were involved in activities of the nervous and sensory systems. Enrichment analysis indicated that genes in these pathways contributed to diabetes or pain. In conclusion, our study enriched the role of DNA methylation in DNP.