Metastudy of potential key genes associated with cardiac fibrosis after acute myocardial infarction from published microarray data in a mouse model

In this study, we investigated the shared key genes, pathway networks, and transcription factors (TFs) associated with Cardiac Fibrosis following Acute Myocardial Infarction (AMI) in mouse models. Gene expression profiles of AMI and the sham-control group were obtained from the series GSE775 and GSE4648 downloaded from the NCBI GEO database. Commonly differentially expressed genes (DEGs) between the AMI groups and the sham-control groups were identified at various time points post-AMI. The DEGs' biological functions, hub genes, and transcription factors (TFs) were explored through integrated bioinformatics tools. After the analysis, at 1 hour, no DEGs were found. At 4h, only 6 upregulated DEGs were identified, with no down-regulated DEGs. At 24h, a total of 260 DEGs were found, including 247 upregulated genes and 13 downregulated genes. At 48h, a total of 302 DEGs were identified, 278 upregulated and 24 downregulated. Functional enrichment analysis revealed that at 4h, the DEGs were primarily involved in "skeletal muscle cell differentiation," "transcription factor binding," and "MAPK signaling pathway." At 24h, the DEGs were primarily associated with "inflammatory response," "external side of the plasma membrane," "cell adhesion molecule binding," and "IL-17 signaling pathway." At 48h, the DEGs were found to be related to "inflammatory response," "membrane raft," "actin binding," and "IL-17 signaling pathway." Based on the PPI network, only six hub genes were identified at 4h, while ten hub genes were identified at 24h and 48h. We then further identified common hub genes at 24h and 48h related to cardiac fibrosis (IL1b, Itgam, Mmp9, Ccl2, IL6, and Ptgs2) which we believe may prove particularly critical in the cardiac fibrosis process. TRRUST predicted several TFs that regulate the hub genes at different time points, including transformation-related protein 53 (Trp53) at 4 hours, Nfkb1 at 24h, and Jun proto-oncogene (Jun) at 48h. These findings from our study offer new perspectives on the molecular mechanisms and potential biomarker targets for treatments against cardiac fibrosis. The findings may also contribute to the future development of optimal "time-to-treatment" strategies for patients with AMI. However, further molecular biological experiments are necessary to validate and confirm these findings.
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