IDENTIFICATION OF POTENTIAL KEY GENES ASSOCIATED WITH CARDIAC FIBROSIS BY RNA SEQUENCING DATA ANALYSIS

DANDAN LIU, HAIZHU WANG, XIAO HAN, CAIPING HAN, FENGBO REN

Department of Cardiology, Zhoukou Central Hospital, Zhoukou 466000, Henan, China

Introduction: Cardiac fibrosis is central to a broad constellation of cardiovascular diseases with similar pathophysiologic companions, and is associated with cardiac dysfunction, arrhythmogenesis, and adverse outcome. However, the option of effective treatment strategies is limited due to the insufficient understanding of the mechanisms for cardiac fibrosis.

Materials and methods: The RNA sequencing data (GSE97358) comprising 84 TGF-????1-stimulated samples and 84 paired unstimulated samples of cultured primary human cardiac fibroblast from GEO database was used to explore crucial genes and pathways involved in cardiac fibrosis. The differentially expressed genes (DEGs) were identified using edgeR package in R. Protein-protein interaction (PPI) network and module analyses were performed and visualized using STRING and Cytoscape. GO (gene ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed by clusterprofiler. The hub genes extracted from PPI were identified by the CytoHubba plug-in and the transcription factor(TF)-hub gene network was further constructed by the iRegulon plug-in.

Results: Totally, 647 DEGs were initially screened out in TGF-????1-stimulated primary human cardiac fibroblast. Twenty hub genes (9 up-regulated: S1PR5, F2RL3, GPR68, CXCR5, KISS1, GAL, LPAR5, HTR1D, PLCB4; 11 down-regulated: CXCL1, GPR65, CYSLTR2, EDNRA, CXCL6, F2R, GNG2 F2RL2, SSTR1, TAS2R1, HTR2B) were further identified. Wnt signaling and neuroactive ligand-receptor interaction signaling pathways enriched were ultimately identified as the key pathways involved in cardiac fibrosis. Seven TFs (RELB, FOS, SREBF2, PURA, TBX21, IRF1 and IRF4) were identified for the TF-hub gene networks.

Conclusions: Our results may provide novel insights into the molecular mechanisms and treatments of cardiac fibrosis. However, further molecular biological experiments are required to confirm these findings.