当前位置: X-MOL 学术Front. Mol. Neurosci. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Identification of Differentially Expressed Genes and Key Pathways in the Dorsal Root Ganglion After Chronic Compression.
Frontiers in Molecular Neuroscience ( IF 4.8 ) Pub Date : 2020-05-05 , DOI: 10.3389/fnmol.2020.00071
Zhanhui Du 1, 2 , Sen Yin 3 , Xiuhui Song 4 , Lechi Zhang 5 , Shouwei Yue 1 , Xiaofeng Jia 6, 7, 8 , Yang Zhang 1, 6
Affiliation  

Neuropathic pain (NP) is caused by primary or secondary impairment of the peripheral or central nervous systems. Its etiology is complex and involves abnormal patterns of gene expression and pathway activation. Using bioinformatics analysis, we aimed to identify NP-associated changes in genes and pathways in L4 and L5 dorsal root ganglia (DRG) in a rat model of NP induced by chronic compression of the DRG (CCD). Genome-wide transcriptional analyses were used to elucidate the molecular mechanisms underlying NP. We screened differentially expressed genes (DEGs) 7 days after CCD in comparison with sham-operated controls. Quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting were used to confirm the presence of key DEGs. Kyoto Encyclopedia of Genes and Genomes (KEGG)-pathway analysis of DEGs and global signal transduction network analysis of DEGs were also conducted. The CCD group developed clear mechanical and thermal allodynia in the ipsilateral hind paw compared with the sham group. This comparison identified 1,887 DEGs, with 1156 upregulated and 731 downregulated DEGs, and 123 DEG-enriched pathways. We identified the key candidate genes that might play a role in the development of NP, namely syndecan 1 (Sdc1), phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit gamma (Pi3k), Janus kinase 2 (Jak2), jun proto-oncogene, AP-1 transcription factor subunit (Jun), and interleukin 6 (IL-6) by analyzing the global signal transduction network. RT-qPCR and western blot analysis confirmed the microarray results. The DEGs Sdc1, Pi3k, Jak2, Jun, and IL-6, and the cytokine signaling pathway, the neuroactive ligand-receptor interaction, the toll-like receptor signaling pathway, and the PI3K-Akt signaling pathway may have decisive modulatory roles in both nerve regeneration and NP. These results provide deeper insight into the mechanism underlying NP and promising therapeutic targets for its treatment.

中文翻译:

慢性压迫后背根神经节中差异表达基因和关键途径的鉴定。

神经性疼痛(NP)由周围或中枢神经系统的原发或继发性损伤引起。其病因复杂,涉及基因表达和途径激活的异常模式。使用生物信息学分析,我们旨在鉴定由慢性压缩DRG(CCD)诱发的NP大鼠模型中L4和L5背根神经节(DRG)的基因和途径中与NP相关的变化。全基因组转录分析被用来阐明NP的分子机制。与假手术对照相比,我们在CCD后7天筛选了差异表达基因(DEG)。实时定量聚合酶链反应(RT-qPCR)和蛋白质印迹法被用来确认关键DEG的存在。还进行了《京都基因与基因组百科全书》(KEGG)-DEG的途径分析和DEG的全局信号转导网络分析。与假手术组相比,CCD组患侧后爪出现明显的机械和热异常性疼痛。该比较确定了1,887个DEG,其中1156个DEG上调和731个下调,以及123个DEG富集的途径。我们确定了可能在NP的发展中起作用的关键候选基因,即syndecan 1(Sdc1),磷脂酰肌醇-4,5-二磷酸3激酶,催化亚基γ(Pi3k),Janus激酶2(Jak2),jun通过分析全球信号转导网络,发现原癌基因,AP-1转录因子亚基(Jun)和白介素6(IL-6)。RT-qPCR和蛋白质印迹分析证实了微阵列结果。DEG Sdc1,Pi3k,Jak2,Jun和IL-6,细胞因子信号通路,神经活性配体-受体相互作用,toll​​样受体信号通路和PI3K-Akt信号通路可能在神经再生和NP中起决定性的调节作用。这些结果提供了更深入的了解NP的潜在机制和有希望的治疗靶标。
更新日期:2020-05-05
down
wechat
bug