Identification of potential hub genes and drugs in septic kidney injury: a bioinformatic analysis with preliminary experimental validation.

BACKGROUND

Sepsis-associated kidney injury (SAKI) is a prevalent complication in intensive care unit (ICU) patients with sepsis. Diagnosis currently relies on clinical assessment, urine output, and serum creatinine levels, yet effective clinical treatments remain scarce. Our objectives are to explore prospective, targeted medications for the treatment of septic kidney injury and to employ bioinformatics to identify key genes and pathways that may be implicated in the pathogenesis of SAKI.

METHODS

We utilized the GEO database for differential gene screening. Related genes of septic kidney injury were identified through Pubmed2Ensembl, followed by annotation and visualization of gene ontology biological processes and KEGG pathways using DAVID. Protein-protein interactions were analyzed with the STRING database, and hub genes were identified using Cytoscape software. Candidate genes were further validated through Metascape. The CTD database was employed to uncover the relationship between hub genes and acute kidney injury (AKI). CIBERSORT was applied to evaluate the infiltration of immune cells and their association with hub genes. Hub genes were experimentally verified through qPCR detection. Lastly, the Drug-Gene Interaction Database (DGIdb) was utilized to identify drug-gene interactions.

RESULTS

Six genes, including TNF, CXCL8, IL-6, IL-1β, IL-2, and IL-10, were associated with three major signaling pathways: the COVID-19 adverse outcome pathway, an overview of pro-inflammatory and pro-fibrotic mediators, and the interleukin-10 signaling pathway. Additionally, 12 targeted drugs were identified as potential therapeutic agents.