Department of Neurosurgery, Fuyang Hospital of Anhui Medical University, No.99 Huangshan Road, Fuhe Modern Industrial Park, Yingzhou District, Fuyang, 236000, Anhui Province, China.
Department of Rehabilitation, Shanghai General Hospital, Shanghai Jiaotong University, Shanghai, 200080, China.
J Mol Neurosci. 2020 Sep;70(9):1345-1353. doi: 10.1007/s12031-020-01549-0. Epub 2020 May 13.
This study aimed to explore the detailed molecular mechanism and biomarkers in spinal cord injury (SCI). Gene expression profiles of GSE125630 were downloaded from the Gene Expression Omnibus (GEO) database, and comprised 14 spinal cord tissues, including contusion SCI group (n = 6, unexercised), complete transection group (n = 4, unexercised), and uninjured control group (n = 4, unexercised). Differentially expressed gene (DEG) and time-series gene investigations, functional enrichment analysis, protein-protein interaction (PPI) network construction, characteristic gene-related disease analysis, and TF-target gene interaction studies were performed. A total of 122 DEGs and 409 DEGs were respectively identified in contusion SCI versus control group and complete transection versus control group, respectively. The PPI network investigated 16 characteristic genes including corticotropin-releasing hormone (CRH), tyrosine hydroxylase (TH), and neurotensin (NTS). These genes were mainly enriched in functions involving response to ethanol, corticosterone, and estradiol. Eventually, a TF-target gene interaction network was constructed with nine TFs [including activating transcription factor 3 (ATF3)] and 10 characteristic genes. The results indicate that regulation of osteoblast differentiation and positive regulation of the BMP signaling pathway may be suppressed in the process of SCI. TH may play a pivotal role in the progression of SCI. In addition, DEGs such as CRH and NTS may be novel targets for SCI therapy.
本研究旨在探讨脊髓损伤（SCI）的详细分子机制和生物标志物。从基因表达综合数据库（GEO）下载了 GSE125630 的基因表达谱，包含 14 个脊髓组织，包括挫伤 SCI 组（n=6，未运动）、完全横断组（n=4，未运动）和未损伤对照组（n=4，未运动）。进行了差异表达基因（DEG）和时间序列基因研究、功能富集分析、蛋白质-蛋白质相互作用（PPI）网络构建、特征基因相关疾病分析和 TF-靶基因相互作用研究。在挫伤 SCI 与对照组和完全横断与对照组的比较中，分别鉴定出 122 个 DEG 和 409 个 DEG。PPI 网络研究了包括促肾上腺皮质激素释放激素（CRH）、酪氨酸羟化酶（TH）和神经降压素（NTS）在内的 16 个特征基因。这些基因主要富集在涉及对乙醇、皮质酮和雌二醇的反应的功能中。最终，构建了一个包含九个 TF（包括激活转录因子 3（ATF3））和 10 个特征基因的 TF-靶基因相互作用网络。结果表明，在 SCI 过程中，成骨细胞分化的调节和 BMP 信号通路的正调控可能受到抑制。TH 可能在 SCI 的进展中发挥关键作用。此外，CRH 和 NTS 等 DEG 可能是 SCI 治疗的新靶点。
