脊髓损伤后肌肉萎缩基因谱的生物信息学分析

Bioinformatics analysis of gene spectrum of muscle atrophy after spinal cord injury

背景:脊髓损伤后常伴随肌肉萎缩的发生,但是它的基本机制仍然不是十分清楚。目的:旨在探讨脊髓损伤后肌肉萎缩的分子生物学机制。方法:分析基因表达数据库中的脊髓损伤后肌肉萎缩的基因谱GSE45550。基因表达谱GSE45550包括对照组(脊髓损伤前)、实验组1(脊髓损伤后3 d)、实验组2(脊髓损伤后8 d)、实验组3(脊髓损伤后14 d)。组织为SD大鼠的比目鱼肌,每组6例。随后对4组样本数据进行差异基因分析、GO分析、通路分析。结果与结论:确定了2 513个差异表达基因,其中Wnt16、Obfc1、Ufd1l、LOC100361067、Hhatl、Fxyd1、Psmc4、Tasp1、Mettl21c、Ufd1l差异表达最显著。GO分析显示差异基因的主要生物学过程为biological_process、G蛋白偶联受体信号通路、对药物的反应、DNA依赖性转录、DNA依赖性转录的正调节、氧化还原过程、泛素依赖性蛋白分解代谢过程、凋亡过程、RNA聚合酶转录的正调控及脂肪酸β-氧化。信号通路如MAPK信号、细胞凋亡、柠檬酸循环(TCA循环)可能起到重要的作用。研究比较完整地揭示了脊髓损伤后肌肉萎缩基因谱的差异表达基因和所涉及的生物学过程和信号通路,其中Wnt16可能是脊髓损伤后肌肉萎缩中的关键基因,为未来的治疗进展提供分子靶点。

BACKGROUND: Muscle atrophy is often associated with spinal cord injury, but its underlying mechanisms are still unclear.OBJECTIVE: To explore the molecular biological mechanism of muscle atrophy after spinal cord injury.METHODS: Gene profile GSE45550 for muscle atrophy after spinal cord injury in the gene expression database was analyzed. The gene expression profile GSE45550 included a control group(pre-spinal cord injury), an experimental group 1(3 days after spinal cord injury), an experimental group 2(8 days after spinal cord injury), and an experimental group 3(14 days after spinal cord injury). The tissue was the soleus muscle of Sprague-Dawley rats(n=6/group). Four groups of sample data were then subjected to differential gene analysis, GO analysis, and pathway analysis.RESULTS AND CONCLUSION: Totally 2 513 differentially expressed genes were identified, of which Wnt16 Obfc1, Ufd1l, LOC100361067,Hhatl, Fxyd1, Psmc4, Tasp1, Mettl21c, and Ufd1l differential expressions were most significant. Biological processes such as biological process, G-protein coupled receptor signaling pathway, response to drug, transcription DNA-dependent, positive regulation of transcription DNA-dependent, oxidation-reduction process, ubiquitin-dependent protein catabolic process, apoptotic process, positive regulation of transcription from RNA polymeras, and fatty acid beta-oxidation, signaling pathways such as MAPK signaling, apoptosis, and citric acid cycle may play important roles. This study completely reveals the differentially expressed genes of muscle atrophy after spinal cord injury gene profiles, the involved biological processes, and signaling pathways. Wnt16 may be a key gene in muscle atrophy after spinal cord injury,providing molecular targets for future therapeutic progress.