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脊髓损伤后不同时间点的再生和枢纽基因及通路的鉴定。

Identification of Regeneration and Hub Genes and Pathways at Different Time Points after Spinal Cord Injury.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, #218 Jixi Road, Hefei, 230022, Anhui Province, China.

Department of Orthopedics, The Third Affiliated Hospital of Anhui Medical University, Hefei, Anhui Province, China.

出版信息

Mol Neurobiol. 2021 Jun;58(6):2643-2662. doi: 10.1007/s12035-021-02289-x. Epub 2021 Jan 23.

Abstract

Spinal cord injury (SCI) is a neurological injury that can cause neuronal loss around the lesion site and leads to locomotive and sensory deficits. However, the underlying molecular mechanisms remain unclear. This study aimed to verify differential gene time-course expression in SCI and provide new insights for gene-level studies. We downloaded two rat expression profiles (GSE464 and GSE45006) from the Gene Expression Omnibus database, including 1 day, 3 days, 7 days, and 14 days post-SCI, along with thoracic spinal cord data for analysis. At each time point, gene integration was performed using "batch normalization." The raw data were standardized, and differentially expressed genes at the different time points versus the control were analyzed by Gene Ontology enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene set enrichment analysis. A protein-protein interaction network was then built and visualized. In addition, ten hub genes were identified at each time point. Among them, Gnb5, Gng8, Agt, Gnai1, and Psap lack correlation studies in SCI and deserve further investigation. Finally, we screened and analyzed genes for tissue repair, reconstruction, and regeneration and found that Anxa1, Snap25, and Spp1 were closely related to repair and regeneration after SCI. In conclusion, hub genes, signaling pathways, and regeneration genes involved in secondary SCI were identified in our study. These results may be useful for understanding SCI-related biological processes and the development of targeted intervention strategies.

摘要

脊髓损伤(SCI)是一种神经系统损伤,可导致损伤部位周围神经元丢失,并导致运动和感觉功能缺陷。然而,其潜在的分子机制尚不清楚。本研究旨在验证 SCI 中的差异基因时程表达,并为基因水平研究提供新的见解。我们从基因表达综合数据库(GEO)中下载了两个大鼠表达谱(GSE464 和 GSE45006),包括 SCI 后 1 天、3 天、7 天和 14 天,以及胸段脊髓数据进行分析。在每个时间点,使用“批量归一化”进行基因整合。对原始数据进行标准化,通过基因本体论富集分析、京都基因与基因组百科全书通路分析和基因集富集分析,分析不同时间点与对照相比的差异表达基因。然后构建并可视化蛋白质-蛋白质相互作用网络。此外,在每个时间点都鉴定出了十个枢纽基因。其中,Gnb5、Gng8、Agt、Gnai1 和 Psap 在 SCI 中缺乏相关性研究,值得进一步研究。最后,我们筛选和分析了与组织修复、重建和再生相关的基因,发现 Anxa1、Snap25 和 Spp1 与 SCI 后修复和再生密切相关。总之,本研究鉴定了参与二次 SCI 的枢纽基因、信号通路和再生基因。这些结果可能有助于理解 SCI 相关的生物学过程,并为开发有针对性的干预策略提供参考。

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