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分析和实验验证在中间阶段挫伤的大鼠脊髓中的基因及其转录因子的预测。

Analysis and experimental validation of genes and their transcription factor prediction in contused rat spinal cord at the intermediate phase.

机构信息

Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, P.R. China.

International Science and Technology Cooperation Base of Spinal Cord Injury, Tianjin Key Laboratory of Spine and Spinal Cord, Tianjin, P.R. China.

出版信息

Aging (Albany NY). 2024 Jun 8;16(11):9990-10003. doi: 10.18632/aging.205912.

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)的中间阶段是治疗 SCI 的重要靶位。然而,对于 SCI 中间阶段的机制尚缺乏深入了解。本研究旨在探讨 SCI 中间阶段的分子机制及可行的治疗靶点。我们从 GEO 下载了 GSE2599 数据集,并鉴定出 416 个显著差异表达基因(DEGs),包括 206 个下调和 210 个上调 DEGs。进一步对 DEGs 的富集分析显示,在受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,并鉴定出前 10 个高连接度的枢纽节点。此外,还鉴定出 27 个预测转录因子(TFs)和 136 个预测基序。然后,我们选择胰岛素样生长因子 1(IGF1)及其预测转录因子,线粒体转录因子 A(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。这些发现为我们提供了关于 SCI 中间阶段病理生理过程的新信息,可能有助于我们更好地理解这一过程。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f12b/11210225/f875809be32c/aging-16-205912-g001.jpg

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