Related Experiment Video
Updated: Jul 9, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Integrated Analysis of Ferroptosis and Immunity-Related Genes Associated with Diabetic Kidney Disease
Jingjing Wang1, Lin Wang1, Zhe Pang1
1Department of Nephropathy, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230022, People's Republic of China.
Purpose:
Diabetic kidney disease (DKD) is the leading cause of chronic kidney disease (CKD) worldwide. Elucidation of the molecular mechanisms underlying ferroptosis and immunity in DKD could aid the development of potentially effective therapeutics. This study aimed to perform an integrated analysis of ferroptosis and immune-related differentially expressed mRNAs (DEGs) in DKD.
Materials And Methods:
Gene expression profiles of samples obtained from patients with DKD and controls were downloaded from the Gene Expression Omnibus (GEO) database. The potential differentially expressed genes (DEGs) were screened using R software, and ferroptosis immune-related differentially expressed genes (FIRDEGs) were extracted from the DEGs. We performed functional enrichment analyses, and constructed protein-protein interaction (PPI) networks, transcription factor (TFs)-gene networks, and gene-drug networks to explore their potential biological functions. Correlation analysis and receiver operating characteristic curves were used for evaluating the FIRDEGs. We used the CIBERSORT algorithm to examine the composition of immune cells and determine the relationship between FIRDEG signatures and immune cells. Finally, the RNA expression of six FIRDEGs was validated in animal kidney samples using RT-PCR.
Results:
We identified 80 FIRDEGs and performed their functional analyses. We identified six hub genes (Ccl5, Il18, Cybb, Fcgr2b, Myd88, and Ccr2) using PPI networks and predicted potential TF gene networks and gene-drug pairs. Immune cells, including M2 macrophages, resting mast cells, and gamma-delta T cells, were altered in DKD; the FIRDEGs (Fcgr2b, Cybb, Ccr2, and Ccl5) were closely correlated with the infiltration abundance of M2 macrophages and gamma-delta T cells. Finally, the hub genes were verified in mouse kidney samples.
Conclusion:
We identified six hub FIRDEGs (Ccl5, Il18, Cybb, Fcgr2b, Myd88, and Ccr2) in DKD, and predicted the potential transcription factor gene networks and possible treatment targets for future research.
Insights
This study identifies six key ferroptosis and immune-related genes in diabetic kidney disease (DKD). These genes offer potential therapeutic targets for treating DKD, a major cause of chronic kidney disease.
Area of Science:
- Nephrology
- Immunology
- Molecular Biology
Background:
- Diabetic kidney disease (DKD) is the primary cause of chronic kidney disease (CKD) globally.
- Understanding the molecular interplay between ferroptosis and immunity in DKD is crucial for developing novel therapeutics.
Purpose of the Study:
- To conduct an integrated analysis of ferroptosis and immune-related differentially expressed messenger RNAs (mRNAs) in DKD.
- To identify key genes and pathways involved in the pathogenesis of DKD.
Main Methods:
- Utilized gene expression profiles from the Gene Expression Omnibus (GEO) database for DKD and control samples.
- Performed differential gene expression analysis, functional enrichment, and constructed protein-protein interaction (PPI), transcription factor (TF)-gene, and gene-drug networks.
- Validated RNA expression of key genes in animal kidney samples using RT-PCR.
Main Results:
- Identified 80 ferroptosis immune-related differentially expressed genes (FIRDEGs) and six hub genes (Ccl5, Il18, Cybb, Fcgr2b, Myd88, Ccr2).
- Discovered significant alterations in immune cell composition in DKD, with specific FIRDEGs correlating with M2 macrophage and gamma-delta T cell infiltration.
- Validated the expression of hub genes in mouse kidney samples.
Conclusions:
- Six hub FIRDEGs were identified in DKD, highlighting their potential roles in disease pathogenesis.
- Predicted transcription factor networks and gene-drug interactions provide potential therapeutic targets for future research in DKD.
