Transcriptome and weighted gene co-expression network analysis identify hub genes and pathways in rat kidneys after deep hypothermic circulatory arrest.

BACKGROUND

Acute kidney injury (AKI) is a frequent and severe complication following aortic dissection repair surgery that utilizes deep hypothermic circulatory arrest (DHCA). This study aimed to identify key hub genes and elucidate the molecular pathways involved in DHCA-associated AKI (DHCA-AKI).

METHODS

A rat model of DHCA was established, and kidney tissues were harvested for high-throughput transcriptome sequencing. Differentially expressed genes (DEGs) between DHCA and control groups were identified using three independent analytical methods (DESeq2, limma, edgeR). Hub genes were subsequently screened by integrating weighted gene co-expression network analysis (WGCNA) and protein-protein interaction (PPI) network analysis. The iRegulon plugin was used to predict upstream regulators. Kidney function markers and the expression levels of identified hub genes were experimentally validated.

RESULTS

We identified 154 significant DEGs (80 up- and 74 down-regulated) and 209 key module genes via WGCNA. Ten hub genes were pinpointed: Jun, Atf3, Cebpb, Il-1β, Nfκbia, Ptgs2, Cxcl1, Nfκbiz, Zfp36, and Tnfaip3. These genes are predominantly associated with inflammatory responses and apoptotic processes. RELA and ATF3 were identified as potential upstream transcriptional regulators. Experimental validation confirmed significant kidney impairment and the substantial upregulation of these hub genes at both mRNA and protein levels following DHCA.

CONCLUSION

DHCA markedly alters the transcriptional landscape in rat kidney tissues. Hub genes and pathways related to inflammation and apoptosis may constitute central pathogenic mechanisms and represent promising therapeutic targets for DHCA-AKI.