Transcriptome profiling and weighted gene co-expression network analysis reveal changes of hub genes and molecular pathways in rat lungs following deep hypothermic circulatory arrest.

BACKGROUND: The incidence of acute lung injury (ALI) following aortic dissection repair surgery that involves deep hypothermic circulatory arrest (DHCA) is notably high. We analyzed hub genes and signaling pathways in rat lung tissues post-DHCA using transcriptome sequencing and weighted gene co-expression network analysis (WGCNA). METHODS: A rat model of DHCA was established, and lung tissues were collected after the procedure. High-throughput transcriptome sequencing was employed to assess gene expression differences between the DHCA group and the non-DHCA group. The DESeq2 method was utilized to analyze differentially expressed genes (DEGs) between these two groups, with further screening for hub genes and their upstream molecules conducted using WGCNA, protein-protein interaction (PPI) networks, and the iRegulon plugin. Biological functions of hub genes were examined via Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses. The changes in mRNA and protein levels of hub genes across both groups were evaluated through experimental verification. RESULTS: A total of 438 DEGs were identified when comparing the DHCA group to the control group. WGCNA further revealed 197 key genes. Subsequent PPI analysis led to the identification of eight hub genes: FOS, FOSB, JUN, EGR1, ATF3, NR4A1, CCN1, and ZFP36. The hub genes were primarily associated with inflammation, cell apoptosis, and cellular immune responses. ATF3 and SRF may serve as potential upstream regulators. The experimental findings further corroborated that substantial alterations took place in these hub genes, accompanied by significant injury of lung tissue during DHCA. CONCLUSION: DHCA significantly altered gene expression patterns in rat lung tissues. The identified hub genes and signaling pathways related to inflammation and apoptosis may serve as potential therapeutic targets for lung injury following DHCA.