Identification of Hub Genes and Pathways in a Rat Model of Renal Ischemia-Reperfusion Injury Using Bioinformatics Analysis of the Gene Expression Omnibus (GEO) Dataset and Integration of Gene Expression Profiles

Med Sci Monit. 2019 Nov 8:25:8403-8411. doi: 10.12659/MSM.920364.

Abstract

BACKGROUND This study aimed to identify hub genes and pathways in a rat model of renal ischemia-reperfusion injury (IRI) using bioinformatics analysis of the Gene Expression Omnibus (GEO) microarray dataset and integration of gene expression profiles. MATERIAL AND METHODS GEO software and the GEO2R calculation method were used to analyze two mRNA profiles, including GSE 39548 and GSE 108195. The co-expression of differentially expressed genes (DEGs) were identified and searched in the DAVID and STRING databases for pathway and protein-protein interaction (PPI) analysis. Cytoscape was used to draw the PPI network. DEGs were also analyzed using the Molecular Complex Detection (MCODE) algorithm. Cytoscape and cytoHubba were used to analyze the hub genes and visualize the molecular interaction networks. Rats (n=20) included the IRI model group (n=10) and a control group (n=10). Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to measure and compare the expression of the identified genes in rat renal tissue in the IRI model and the control group. RESULTS Ten hub genes were identified, STAT3, CD44, ITGAM, CCL2, TIMP1, MYC, THBS1, IGF1, SOCS3, and CD14. Apart from IGF1, qRT-PCR showed that expression of these genes was significantly increased in renal tissue in the rat model of IRI. The HIF-1alpha signaling pathway was involved in IRI in the rat model, which was supported by MCODE analysis. CONCLUSIONS In a rat model of renal IRI, bioinformatics analysis of the GEO dataset and integration of gene expression profiles identified involvement of HIF-1alpha signaling and the STAT3 hub gene.

MeSH terms

  • Animals
  • Biomarkers, Tumor / genetics
  • China
  • Computational Biology / methods
  • Disease Models, Animal
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics
  • Gene Ontology
  • Gene Regulatory Networks / genetics
  • Kidney / metabolism*
  • Kidney / pathology
  • Male
  • Protein Interaction Maps / genetics
  • Rats
  • Reperfusion Injury / genetics*
  • Reperfusion Injury / metabolism*
  • Software
  • Transcriptome / genetics

Substances

  • Biomarkers, Tumor