Metabolic Reprogramming in Spinal Cord Injury and Analysis of Potential Therapeutic Targets

IF 2.8 4区 医学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Xiangjun Chen, Juan Wang, Peiran Chan, Qian Zhu, Ziyan Zhu, Mingming Zheng, Xinyi Chen, Haozhen Wu, Min Cui, Yongjie Zhang
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Abstract

Spinal cord injury (SCI) is a critical neurological disorder that frequently leads to permanent disability, profoundly affecting the quality of life of individuals with SCI. In this research, we examined the varied expression of genes associated with metabolic reprogramming–related genes in SCI. By employing the Gene Expression Omnibus datasets GSE5296 and GSE47681, 1001 differentially expressed genes (DEGs) were identified through the limma R package. Among these, 871 and 130 genes were upregulated and downregulated, respectively. A subset of 10 metabolic reprogramming–related differentially expressed genes (MRRDEGs) was recognized as key players in metabolic reprogramming. Analyses of enrichment performed using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes indicated that the identified MRRDEGs predominantly participated in processes related to pyruvate metabolism and carbohydrate degradation. Nine hub genes were discerned using a protein–protein interaction network. Subsequently, an SCI mouse model was established using the LISA SCI modeling device, and preliminary validation was conducted through quantitative real-time PCR experiments at various time points after SCI, specifically on days 1, 3, and 7, suggesting their central role in SCI. Receiver operating characteristic curve analysis indicated that these MRRDEGs could be used to diagnose SCI. The CIBERSORT algorithm analysis of immune infiltration identified an inverse relationship between M0 and M2 macrophages. Furthermore, a positive relationship was observed between Ucp2 and M0 macrophages, underscoring their essential function in the immune response following SCI. These results highlight MRRDEGs’ importance in SCI and propose their potential roles as targets for therapeutic interventions.

Graphical Abstract

Using data from the public GEO database, we identified differentially expressed genes associated with metabolic reprogramming in spinal cord injury and successfully validated them through qPCR experiments.

脊髓损伤中的代谢重编程及其潜在治疗靶点分析
脊髓损伤(SCI)是一种严重的神经系统疾病,经常导致永久性残疾,严重影响SCI患者的生活质量。在这项研究中,我们检测了SCI中代谢重编程相关基因的不同表达。利用基因表达综合数据库GSE5296和GSE47681,通过limma R包鉴定出1001个差异表达基因(deg)。其中上调基因871个,下调基因130个。10个代谢重编程相关的差异表达基因(MRRDEGs)被认为是代谢重编程的关键参与者。利用基因本体和京都基因与基因组百科全书进行的富集分析表明,鉴定的mrrdeg主要参与与丙酮酸代谢和碳水化合物降解相关的过程。利用蛋白质相互作用网络识别出9个枢纽基因。随后,利用LISA SCI建模装置建立SCI小鼠模型,并在SCI发生后的不同时间点,特别是第1、3、7天,通过实时荧光定量PCR实验进行初步验证,提示其在SCI中的核心作用。受试者工作特征曲线分析表明,这些mrrdeg可用于脊髓损伤的诊断。免疫浸润的CIBERSORT算法分析发现M0与M2巨噬细胞呈反比关系。此外,Ucp2和M0巨噬细胞之间存在正相关,强调了它们在脊髓损伤后免疫反应中的重要作用。这些结果突出了MRRDEGs在脊髓损伤中的重要性,并提出了它们作为治疗干预靶点的潜在作用。利用公共GEO数据库的数据,我们确定了与脊髓损伤代谢重编程相关的差异表达基因,并通过qPCR实验成功验证了它们。
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来源期刊
Journal of Molecular Neuroscience
Journal of Molecular Neuroscience 医学-神经科学
CiteScore
6.60
自引率
3.20%
发文量
142
审稿时长
1 months
期刊介绍: The Journal of Molecular Neuroscience is committed to the rapid publication of original findings that increase our understanding of the molecular structure, function, and development of the nervous system. The criteria for acceptance of manuscripts will be scientific excellence, originality, and relevance to the field of molecular neuroscience. Manuscripts with clinical relevance are especially encouraged since the journal seeks to provide a means for accelerating the progression of basic research findings toward clinical utilization. All experiments described in the Journal of Molecular Neuroscience that involve the use of animal or human subjects must have been approved by the appropriate institutional review committee and conform to accepted ethical standards.
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