Related Experiment Video
Updated: Oct 2, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Proteomic Analysis of Mouse Kidney Tissue Associates Peroxisomal Dysfunction with Early Diabetic Kidney Disease
Aggeliki Tserga1, Despoina Pouloudi2, Jean Sébastien Saulnier-Blache3,4
1Department of Biotechnology, Biomedical Research Foundation, Academy of Athens, Soranou Efessiou 4, 11527 Athens, Greece.
Background:
The absence of efficient inhibitors for diabetic kidney disease (DKD) progression reflects the gaps in our understanding of DKD molecular pathogenesis.
Methods:
A comprehensive proteomic analysis was performed on the glomeruli and kidney cortex of diabetic mice with the subsequent validation of findings in human biopsies and omics datasets, aiming to better understand the underlying molecular biology of early DKD development and progression.
Results:
LC-MS/MS was employed to analyze the kidney proteome of 2 DKD models: Ins2Akita (early and late DKD) and db/db mice (late DKD). The abundance of detected proteins was defined. Pathway analysis of differentially expressed proteins in the early and late DKD versus the respective controls predicted dysregulation in DKD hallmarks (peroxisomal lipid metabolism and β-oxidation), supporting the functional relevance of the findings. Comparing the observed protein changes in early and late DKD, the consistent upregulation of 21 and downregulation of 18 proteins was detected. Among these were downregulated peroxisomal and upregulated mitochondrial proteins. Tissue sections from 16 DKD patients were analyzed by IHC confirming our results.
Conclusion:
Our study shows an extensive differential expression of peroxisomal proteins in the early stages of DKD that persists regardless of the disease severity, providing new perspectives and potential markers of diabetic kidney dysfunction.
Insights
Diabetic kidney disease (DKD) progression lacks effective inhibitors due to poor understanding of its molecular causes. This study identifies altered peroxisomal protein expression in early DKD, offering potential new therapeutic targets.
Area of Science:
- Proteomics
- Molecular Biology
- Diabetic Nephropathy Research
Background:
- Diabetic kidney disease (DKD) progression lacks effective inhibitors.
- Understanding DKD molecular pathogenesis is crucial for developing treatments.
Purpose of the Study:
- To investigate the molecular mechanisms of early DKD development and progression.
- To identify potential biomarkers for DKD.
Main Methods:
- Comprehensive proteomic analysis of glomeruli and kidney cortex in diabetic mouse models (Ins2Akita and db/db).
- Validation using human biopsies and omics datasets.
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) and immunohistochemistry (IHC).
Main Results:
- Identified differential expression of 21 upregulated and 18 downregulated proteins in early and late DKD.
- Detected dysregulation in peroxisomal lipid metabolism and beta-oxidation pathways.
- Confirmed downregulation of peroxisomal proteins and upregulation of mitochondrial proteins in human DKD samples.
Conclusions:
- Extensive differential expression of peroxisomal proteins occurs in early DKD.
- These changes persist regardless of disease severity.
- Identified potential novel markers for diabetic kidney dysfunction.
