基因表达谱分析揭示了与扩张型和缺血性心肌病相关的基因和转录因子。

Gene expression profiling reveals genes and transcription factors associated with dilated and ischemic cardiomyopathies.

作者信息

Qiao Aiqing, Zhao Zhenying, Zhang Hui, Sun Zhenyu, Cui Xiao

机构信息

Department of Pharmacy, The Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

School of Chemical Engineering and Technology, Tianjin University, Tianjin, China; Department of Pharmacy, Tianjin Union Medical Center, Tianjin, China.

出版信息

Pathol Res Pract. 2017 May;213(5):548-557. doi: 10.1016/j.prp.2016.12.017. Epub 2016 Dec 29.

DOI:10.1016/j.prp.2016.12.017

PMID:28318762

Abstract

AIMS

Dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) can cause heart failure, and this study aims to identify genes and transcription factors (TFs) associated with DCM and ICM.

METHODS

Gene expression dataset GSE42955 was generated from GEO database, and it contained 12 DCM, 12 ICM, and 5 control samples. Differentially expressed genes (DEGs) were identified between DCM (or ICM) and controls. Gene functions were investigated, and their associations were analyzed using Enrichmentmap plugin in Cytoscape. Protein-protein interactions (PPIs) between DEGs were determined, and DEGs with high degree were defined as key DEGs. Potential TFs of key DEGs were predicted using iRegulon plugin. Common DEGs were found, and their functional interactions were investigated using GeneMANIA.

RESULTS

A total of 362 and 300 DEGs were respectively identified for DCM and ICM in comparison with controls, and these DEGs mainly participated in similar functions about extracellular region, membrane, immune process, and defense response. PPI networks were respectively constructed for DCM and ICM, and 26 key DEGs (e.g. CXCL10, IL6, TLR3, and VCAM1) were found, which might be targeted by 35 TFs (e.g. IRF1). Besides, 47 common up-regulated DEGs were found, which participated in 14 pathways like Apoptosis, Collagen formation, as well as 127 common down-regulated DEGs that involved in 20 pathways like Adaptive immune system, Interferon γ signaling (e.g. IRF1, VCAM1), and Toll-like receptor signaling pathway (e.g. CXCL10, IL6, TLR3).

CONCLUSION

DCM and ICM may share similar mechanism, and TFs (e.g. IRF1) play crucial roles in their development via regulating gene expression.

摘要

目的

扩张型心肌病（DCM）和缺血性心肌病（ICM）可导致心力衰竭，本研究旨在鉴定与DCM和ICM相关的基因和转录因子（TFs）。

方法

从基因表达综合数据库（GEO数据库）生成基因表达数据集GSE42955，其包含12个DCM样本、12个ICM样本和5个对照样本。鉴定DCM（或ICM）与对照之间的差异表达基因（DEGs）。研究基因功能，并使用Cytoscape中的Enrichmentmap插件分析它们之间的关联。确定DEGs之间的蛋白质-蛋白质相互作用（PPIs），将具有高度连接的DEGs定义为关键DEGs。使用iRegulon插件预测关键DEGs的潜在TFs。找出共同的DEGs，并使用GeneMANIA研究它们的功能相互作用。

结果

与对照相比，分别为DCM和ICM鉴定出362个和300个DEGs，这些DEGs主要参与细胞外区域、膜、免疫过程和防御反应等相似功能。分别构建了DCM和ICM的PPI网络，发现26个关键DEGs（如CXCL10、IL6、TLR3和VCAM1），它们可能被35个TFs（如IRF1）靶向。此外，发现47个共同上调的DEGs，它们参与凋亡、胶原蛋白形成等14条通路，以及127个共同下调的DEGs，它们参与适应性免疫系统、干扰素γ信号通路（如IRF1、VCAM1）和Toll样受体信号通路（如CXCL10、IL6、TLR3）等20条通路。