心力衰竭相关新基因的筛选和分析

Screening and analysis of the novel genes related to heart failure

目的分析心力衰竭潜在的相关基因以及相关机制。方法从基因表达综合数据库中下载数据集GSE18703,使用R软件中“limma”包分析差异表达基因(DEGs)。对DEGs进行基因本体论(GO)和京都基因和基因组百科全书(KEGG)通路富集分析,以探索心力衰竭相关的生物学功能和信号通路。使用Cytoscape软件构建蛋白质相互作用(PPI)网络,识别心力衰竭发病机制相关的关键基因,用荧光定量聚合酶链反应(qPCR)法对血管紧张素Ⅱ(AngⅡ)诱导的大鼠H9C2心肌细胞模型进行转录水平的验证。通过h TFtarget数据库分析关键基因的转录因子网络,以探究心力衰竭的发生机制。结果共筛选出292个DEGs,其中上调基因140个,下调基因152个。GO分析显示,DEGs主要富集于细胞外区、细胞外空间、血液微粒等细胞成分以及嗅觉转导、血管平滑肌收缩、代谢途径等通路。KEGG通路分析发现,DEGs主要富集于环磷酸鸟苷(cGMP)-蛋白激酶G(PKG)信号通路、肥厚型心肌病和扩张型心肌病等信号通路。通过PPI网络,筛选出6个关键基因,分别是Gprc6a、C3、Anxa1、Oxt、Gpr4和Avpr1b,并发现有528个转录因子对这6个关键基因进行转录调节。qPCR结果显示,心力衰竭情况下Anxa1和Gpr4的mRNA表达差异有统计学意义,进一步验证了以上筛选结果。结论通过生物信息学分析方法发现了6个与心力衰竭相关的关键基因,有助于更好地了解心力衰竭的发生机制和探索新的治疗靶点。

Objective To explore the potential related genes and mechanisms of heart failure.Methods The dataset GSE18703 was downloaded from the Gene Expression Omnibus database(GEO),and Differentially Expressed Genes(DEGs)were analyzed using the"limma"package in R software.GO and KEGG pathway enrichment analysis were performed on DEGs to explore the biological functions and signaling pathways related to heart failure.A protein-protein interaction(PPI)network was constructed using Cytoscape software to identify key genes related to the pathogenesis of heart failure.The transcription levels of screened genes were verified in rat H9C2 cardiomyocytes induced by Ang Ⅱ using qPCR.The transcription factor network of key genes was analyzed through hTFtarget database to further investigate the mechanism of heart failure.Results A total of 292 DEGs were screened out,including 140 up-regulated genes and 152 down-regulated genes.GO analysis revealed that the DEGs were mainly enriched in extracellular regions,extracellular spaces,blood particles and other cellular components,as well as pathways such as olfactory transduction,vascular smooth muscle contraction,and metabolic pathways.KEGG pathway analysis found that DEGs were mainly enriched in cGMP-PKG signaling pathway,hypertrophic cardiomyopathy,dilated cardiomyopathy and other signaling pathways.Through the PPI network,six key genes were identified,namely Gprc6a,C3,Anxa1,Oxt,Gpr4 and Avpr1b.And 528 transcription factors were found to regulate the transcription of these six key genes.The qPCR results showed a significant difference in mRNA expression between Anxa1 and Gpr4 in heart failure,further confirming the above screening results.Conclusion Through bioinformatics analysis,we successfully identified six key genes associated with heart failure,which can help to better understand the mechanism of heart failure and explore novel therapeutic targets.