Identification of Critical Genes and Signaling Pathways in Human Monocytes Following High-Intensity Exercise.

Abstract

Background: Monocytes are critical components, not only for innate immunity, but also for the activation of the adaptive immune system. Many studies in animals and humans have demonstrated that monocytes may be closely associated with chronic inflammatory diseases and be proved to be pivotal in the association between high-intensity exercise and anti-inflammation response. However, the underlying molecular mechanisms driving this are barely understood. The present study aimed to screen for potential hub genes and candidate signaling pathways associated with the effects of high-intensity exercise on human monocytes through bioinformatics analysis. Materials and Methods: The GSE51835 gene expression dataset was downloaded from the Gene Expression Omnibus database. The dataset consists of 12 monocyte samples from two groups of pre-exercise and post-exercise individuals. Identifying differentially expressed genes (DEGs) with R software, and functional annotation and pathway analyses were then performed with related web databases. Subsequently, a protein–protein interaction (PPI) network which discovers key functional protein and a transcription factors-DEGs network which predicts upstream regulators were constructed. Results: A total of 146 differentially expressed genes were identified, including 95 upregulated and 51 downregulated genes. Gene Ontology analysis indicated that in the biological process functional group, these DEGs were mainly involved in cellular response to hydrogen peroxide, response to unfolded protein, negative regulation of cell proliferation, cellular response to laminar fluid shear stress, and positive regulation of protein metabolic process. The top five enrichment pathways in a Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were the FoxO signaling pathway, protein processing in the endoplasmic reticulum, influenza A, the ErbB signaling pathway, and the MAPK signaling pathway. TNF, DUSP1, ATF3, CXCR4, NR4A1, BHLHE40, CDKN1B, SOCS3, TNFAIP3, and MCL1 were the top 10 potential hub genes. The most important modules obtained in the PPI network were performed KEGG pathway analysis, which showed that these genes were mainly involved in the MAPK signaling pathway, the IL-17 signaling pathway, the TNF signaling pathway, osteoclast differentiation, and apoptosis. A transcription factor (TF) target network illustrated that FOXJ2 was a critical regulatory factor. Conclusions: This study identified the essential genes and pathways associated with exercise and monocytes. Among these, four essential genes (TNF, DUSP1, CXCR4, and NR4A1) and the FoxO signaling pathway play vital roles in the immune function of monocytes. High-intensity exercise may improve the resistance of chronic inflammatory diseases by regulating the expression of these genes.