关键词: TFAM differentially expressed genes intermediate phase spinal cord injury transcription factors

Mesh : Animals Spinal Cord Injuries / genetics metabolism Rats Transcription Factors / genetics metabolism Insulin-Like Growth Factor I / genetics metabolism Protein Interaction Maps / genetics Gene Expression Profiling Spinal Cord / metabolism DNA-Binding Proteins / genetics metabolism Gene Regulatory Networks Rats, Sprague-Dawley Gene Expression Regulation Mitochondrial Proteins / genetics metabolism

来  源:   DOI:10.18632/aging.205912   PDF(Pubmed)

Abstract:
The intermediate phase of spinal cord injury (SCI) serves as an important target site for therapeutic mediation of SCI. However, there is a lack of insight into the mechanism of the intermediate phase of SCI. The present study aimed to investigate the molecular mechanism and the feasible treatment targets in the intermediate phase of SCI. We downloaded GSE2599 from GEO and identified 416 significant differentially expressed genes (DEGs), including 206 downregulated and 210 upregulated DEGs. Further enrichment analysis of DEGs revealed that many important biological processes and signal pathways were triggered in the injured spinal cord. Furthermore, a protein-protein interaction (PPI) network was constructed and the top 10 high-degree hub nodes were identified. Furthermore, 27 predicted transcription factors (TFs) and 136 predicted motifs were identified. We then selected insulin-like growth factor 1 (IGF1) and its predicted transcription factor, transcription factor A, mitochondrial (TFAM) for further investigation. We speculated and preliminarily confirmed that TFAM may regulate gene transcription of IGF1 and effected alterations in the function recovery of rats after SCI. These findings together provide novel information that may improve our understanding of the pathophysiological processes during the intermediate phase of SCI.
摘要:
脊髓损伤(SCI)的中期是SCI治疗介导的重要靶位点。然而,对SCI中间阶段的机制缺乏了解。本研究旨在探讨SCI中期的分子机制和可行的治疗靶点。我们从GEO下载GSE2599,鉴定出416个显著的差异表达基因(DEG),包括206个下调的DEG和210个上调的DEG。对DEGs的进一步富集分析表明,在损伤的脊髓中触发了许多重要的生物学过程和信号通路。此外,构建了蛋白质-蛋白质相互作用(PPI)网络,并鉴定了前10个高度枢纽节点.此外,鉴定了27个预测的转录因子(TF)和136个预测的基序。然后我们选择胰岛素样生长因子1(IGF1)及其预测的转录因子,转录因子A,线粒体(TFAM)进行进一步研究。我们推测并初步证实,TFAM可能调节IGF1的基因转录,并影响SCI后大鼠功能恢复的变化。这些发现共同提供了新的信息,可以提高我们对SCI中期病理生理过程的理解。
公众号