脊髓损伤后基因表达变化的时间序列。

The Time Sequence of Gene Expression Changes after Spinal Cord Injury.

机构信息

Department of Nanobiomedical Science & BK21 NBM Global Research Center for Regenerative Medicine, Dankook University, Cheonan 31116, Korea.

Center for Bio Medical Engineering Core Facility, Dankook University, Cheonan 31116, Korea.

出版信息

Cells. 2022 Jul 18;11(14):2236. doi: 10.3390/cells11142236.

Abstract

Gene expression changes following spinal cord injury (SCI) are time-dependent, and an accurate understanding of these changes can be crucial in determining time-based treatment options in a clinical setting. We performed RNA sequencing of the contused spinal cord of rats at five different time points from the very acute to chronic stages (1 hour, 1 day, 1 week, 1 month, and 3 months) following SCI. We identified differentially expressed genes (DEGs) and Gene Ontology (GO) terms at each time point, and 14,257 genes were commonly expressed at all time points. The biological process of the inflammatory response was increased at 1 hour and 1 day, and the cellular component of the integral component of the synaptic membrane was increased at 1 day. DEGs associated with cell activation and the innate immune response were highly enriched at 1 week and 1 month, respectively. A total of 2841 DEGs were differentially expressed at any of the five time points, and 18 genes (17 upregulated and 1 downregulated) showed common expression differences at all time points. We found that interleukin signaling, neutrophil degranulation, eukaryotic translation, collagen degradation, LGI-ADAM interactions, GABA receptor, and L1CAM-ankyrin interactions were prominent after SCI depending on the time post injury. We also performed gene-drug network analysis and found several potential antagonists and agonists which can be used to treat SCI. We expect to discover effective treatments in the clinical field through further studies revealing the efficacy and safety of potential drugs.

摘要

脊髓损伤 (SCI) 后的基因表达变化具有时间依赖性,准确了解这些变化对于确定临床治疗方案的时间选择至关重要。我们对 SCI 后非常急性到慢性阶段的大鼠挫伤脊髓进行了 RNA 测序,共 5 个不同时间点(1 小时、1 天、1 周、1 个月和 3 个月)。我们在每个时间点都鉴定了差异表达基因 (DEG) 和基因本体论 (GO) 术语,共有 14257 个基因在所有时间点都有表达。炎症反应的生物学过程在 1 小时和 1 天增加,突触膜完整成分的细胞成分在 1 天增加。与细胞激活和固有免疫反应相关的 DEG 在 1 周和 1 个月分别高度富集。在任何 5 个时间点中共有 2841 个 DEG 存在差异表达,其中 18 个基因(17 个上调,1 个下调)在所有时间点都表现出共同的表达差异。我们发现白细胞介素信号、嗜中性粒细胞脱颗粒、真核翻译、胶原降解、LGI-ADAM 相互作用、GABA 受体和 L1CAM-锚蛋白相互作用在 SCI 后随时间推移而变得明显。我们还进行了基因-药物网络分析,发现了几种潜在的拮抗剂和激动剂,可用于治疗 SCI。我们期望通过进一步研究揭示潜在药物的疗效和安全性,在临床领域发现有效的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b924/9324287/3aa09e38162c/cells-11-02236-g001.jpg

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