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Identification of Potential Targets Associated With Programmed Cell Death for Acute Kidney Injury Based on WGCNA
1Division of Nephrology & Unit of Critical Nephrology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
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.
Insights
Programmed cell death (PCD) is newly implicated in acute kidney injury (AKI). This study identifies five key PCD genes, DPP4, ATF3, KIT, MSX1, and SNAI2, offering potential therapeutic targets for kidney disease.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Programmed cell death (PCD) pathways, including apoptosis and regulated necrosis, are vital for cell turnover and tissue homeostasis.
- The role of PCD in the pathogenesis of acute kidney disease (AKI) has not been previously explored.
Purpose of the Study:
- To investigate the involvement of PCD pathways in AKI.
- To identify key genes associated with PCD in AKI and explore their correlation with immune responses.
Main Methods:
- Utilized gene expression profiling datasets (GSE139061) from the Gene Expression Omnibus (GEO) database.
- Performed differential gene expression analysis and weighted gene co-expression network analysis (WGCNA) to identify hub genes.
- Employed single sample gene set enrichment analysis (ssGSEA) to correlate hub genes with immune cell infiltration and pathway activation.
- Validated findings using a mouse model of ischemia-reperfusion injury.
Main Results:
- Identified five key genes (DPP4, ATF3, KIT, MSX1, SNAI2) associated with PCD in AKI.
- Demonstrated a correlation between these hub genes and immune cell infiltration and immune pathway activation.
- Confirmed gene expression patterns in a mouse model of ischemia-reperfusion injury.
Conclusions:
- This study is the first to propose the involvement of PCD in the pathogenesis of AKI.
- The identified PCD-related genes may mediate pro-inflammatory immune mechanisms via damage-associated molecular patterns (DAMPs) in AKI.
- These genes represent potential therapeutic targets for AKI treatment.
Related Concept Videos
01:22Acute Kidney Injury I: Introduction
01:29Acute Kidney Injury II: Pathophysiology
01:29Acute Kidney Injury III: Clinical Manifestations
01:30Acute Kidney Injury IV: Diagnostic Studies and Prevention
01:20Acute Kidney Injury V: Interprofessional Care
01:22Acute Kidney Injury VI: Nursing Management