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Updated: May 16, 2026
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Gene networks implicated in diabetic kidney disease
1Department of Endocrinology, The Affiliated Jiangyin Hospital of Southeast University Medical College, Jiangyin, Jiangsu, People's Republic of China. drtangwei@yahoo.com.cn
Background:
Diabetic kidney disease (DKD) is one of the main causes of renal end-stage disease. The incidence of DKD has increased substantially over the past few years. However, our understanding to the molecular mechanism of DKD is still essential, and an effective treatment has not been developed.
Aim:
We aimed to explore the molecule mechanism in the development of DKD, and provide a comparison of DKD in different compartments.
Materials And Methods:
In this study, we implemented a system biology approach and analyzed gene expression profiles in 22 microdissected human renal glomerular and 22 tubule samples from healthy patients and patients with DKD.
Results:
The WGCNA (Weighted Gene Co-expression Network Analysis) analysis identified 10 modules of genes with high topological overlap in tubuli and 12 modules in glomeruli. Several TFs (transcription factors) were found expressed in both compartments, such as ETS1, ETV4, JUN, LITAF, NFE2, RARG and STAT5A. These genes may be used as therapeutic targets for DKD. By comparing the modules in the two compartments, we found that dysregulation of cell proliferation may significantly contribute to the development of DKD. Furthermore, our results concluded that DKD may be an immune-mediated degenerative disease.
Conclusions:
Our studies identified multiple genes that may play an important role in the pathogenesis of DKD and provided a system understanding of the potential relationships among these genes. We hope our study could aid in understanding of DKD and could provide the basis for DKD biomarker discovery.
Insights
Diabetic kidney disease (DKD) involves molecular changes in kidney glomeruli and tubules. This study identifies potential therapeutic targets and suggests DKD is an immune-mediated disease, offering insights for biomarker discovery.
Area of Science:
- Nephrology
- Molecular Biology
- Systems Biology
Background:
- Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease with increasing incidence.
- Understanding the molecular mechanisms of DKD is crucial for developing effective treatments.
- Current knowledge of DKD pathogenesis remains incomplete.
Purpose of the Study:
- To elucidate the molecular mechanisms underlying DKD development.
- To compare molecular changes in different kidney compartments (glomeruli and tubules) in DKD.
- To identify potential therapeutic targets and biomarkers for DKD.
Main Methods:
- A systems biology approach was employed.
- Gene expression profiles were analyzed in microdissected human renal glomerular and tubule samples.
- Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify gene modules.
Main Results:
- WGCNA identified 10 gene modules in tubules and 12 in glomeruli.
- Several transcription factors (TFs) like ETS1, ETV4, JUN, LITAF, NFE2, RARG, and STAT5A were identified in both compartments.
- Dysregulation of cell proliferation and immune-mediated processes were implicated in DKD pathogenesis.
Conclusions:
- Multiple genes crucial for DKD pathogenesis were identified.
- A systems-level understanding of gene relationships in DKD was provided.
- The study offers a basis for DKD biomarker discovery and potential therapeutic strategies.
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