Journal of Shanghai Jiao Tong University (Medical Science) >

2022 , Vol. 42 >Issue 1: 51 - 62

DOI: https://doi.org/10.3969/j.issn.1674-8115.2022.01.008

Basic research

Screening potential hub genes associated with myocardial ischemia-reperfusion injury in mice based on GEO database and bioinformatics analysis

  • Jianru WANG ,
  • Guangcao PENG ,
  • Mingjun ZHU
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  • Department of Cardiology, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450099, China
ZHU Mingjun, E-mail: zhumingjun317@163.com.

Received date: 2021-09-27

  Online published: 2022-01-28

Supported by

National Natural Science Foundation of China(82004311);Key Research and Development and Promotion Special Project of Henan Province (Scientific Problem Tackling) Project(202102310492);Traditional Chinese Medicine Scientific Research Special Project of Henan Province(2019JDZX2013);Postdoctoral Research Project of Henan Province(202001045);Zhongyuan Academician Foundation-Famous Doctor of Zhongyuan

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Abstract

Objective

·To screen the potential hub genes associated with myocardial ischemia-reperfusion injury (MIRI) in mice by bioinformatics analysis based on gene expression omnibus (GEO) database.

Methods

·The mouse MIRI data sets GSE61592, GSE83472 and GSE160516 were obtained from GEO database. The differentially expressed genes (DEGs) in each data set were screened by limma package, and then robust DEGs were screened by robust sorting integration (RRA) method. The protein-protein interaction (PPI) network of robust DEGs was constructed, and the submodules and hub genes in the PPI network were screened. The clusterProfiler package was used to analyze the robust DEGs, the most important submodule genes and hub genes by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). Eighteen male C57BL/6 J mice aged 6?8 weeks were randomly divided into sham group and MIRI group, 9 mice each group. The MIRI model was constructed by left anterior descending coronary artery ligation for 30 min ischemia and 24 h reperfusion, and the mRNA expression of hub genes was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results

·RRA method identified 294 robust DEGs in three data sets. In PPI network, a total of 14 sub-modules were screened, of which module 1 was the most important and 17 hub genes were found. GO and KEGG analysis showed that the robust DEGs, module 1 genes, and the hub genes were mainly involved in regulating the migration of inflammatory cells, the activity of chemokines and cytokines and their receptors, Toll-like receptors and other biological function and signaling pathways. RT-qPCR results showed that compared with the sham group, the expressions of chemokine (C-C motif) ligand 4 (Ccl4), Ccl6, Ccl7, chemokine (C-X-C motif) receptor 4 (Cxcr4), chemokine (C-C motif) receptor 2 (Ccr2), signal-regulatory protein β1 (Sirpb1), low affinity immunoglobulin gamma Fc region receptor Ⅱb (Fcgr2b), leukocyte surface antigen CD53 (Cd53), arachidonate 5-lipoxygenase activating protein (Alox5ap), myeloid differentiation primary response gene 88 (Myd88), macrophage scavenger receptor 1 (Msr1), matrix metallopeptidase 14 (Mmp14), triggering receptor expressed on myeloid cells 2 (Trem2) and leupaxin (Lpxn) were up-regulated in the myocardium of the MIRI group, but there was no difference inlow affinity immunoglobulin gamma Fc region receptor Ⅲ (Fcgr3), complement C1q subcomponent subunit B (C1qb) and a disintegrin and metalloproteinase domain-containing protein 8 (Adam8). By reviewing the literatures, Trem2, Lpxn, Cd53, Alox5ap, Sirpb1 and Fcgr2b were not reported to participate in MIRI.

Conclusion

·This study has unearthed 6 potential hub genes for MIRI in mice, and the results can provide new ideas and entry points for further exploring the molecular mechanism and therapeutic targets of MIRI.

Key words： myocardium ischemia-reperfusion injury (MIRI); bioinformatics analysis; differentially expressed gene (DEG); hub gene; gene expression omnibus

Cite this article

Jianru WANG , Guangcao PENG , Mingjun ZHU . Screening potential hub genes associated with myocardial ischemia-reperfusion injury in mice based on GEO database and bioinformatics analysis[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2022 , 42(1) : 51 -62 . DOI: 10.3969/j.issn.1674-8115.2022.01.008

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