Identification of Potential Targets Associated With Programmed Cell Death for Acute Kidney Injury Based on WGCNA.

Abstract

Programmed cell death (PCD) pathways play a crucial role in maintaining normal cell turnover and tissue homeostasis, encompassing apoptosis and regulated necrosis. However, the involvement of PCD in the pathogenesis of acute kidney disease remains unexplored. In this study, we utilized gene expression profiling datasets (GSE139061) obtained from the Gene Expression Omnibus (GEO) database. Through differential gene expression analysis and weighted gene co-expression network analysis (WGCNA), we identified five key genes associated with PCD, namely DPP4, ATF3, KIT, MSX1, and SNAI2 in acute kidney injury (AKI). Subsequently, single sample gene set enrichment analysis (ssGSEA) was employed to demonstrate the correlation between these five hub genes and immune cell infiltration as well as activation of immune pathways. Furthermore, we validated our findings by analyzing gene expression patterns using a mouse model of ischemia-reperfusion injury. In conclusion, our study is the first to propose the concept of PCD in the pathogenesis of AKI. This finding has significant implications for future investigations into pro-inflammatory immune mechanisms mediated by damage-associated molecular patterns (DAMPs) during the stages of AKI. Our findings underscore the necessity for further investigation into these molecules, which may offer new avenues for therapeutic intervention in AKI. These identified genes may serve as promising targets for intervention in cases of acute kidney diseases.