A common glomerular transcriptomic signature distinguishes diabetic kidney disease from other kidney diseases in humans and mice
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Updated: Dec 19, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Moustafa Abdalla1, Mohamed Abdalla2, Ferhan S Siddiqi3
1Keenan Research Centre for Biomedical Science and Li Ka Shing Knowledge Institute of St. Michael's Hospital, Toronto, Ontario, Canada; University of Toronto, Toronto, Ontario, Canada.
Background:
Current uncertainties about the similarity between human diseases and their experimental models are hampering the development of new therapies. This is especially the case for diabetic kidney disease (DKD), the most common cause of end-stage kidney disease. To better understand the nature of the commonality between humans and their mouse models, we posed the question: in diabetic kidney disease are transcriptional profiles primarily disease-specific or species-specific?
Methods:
We performed a meta-comparison of the glomerular transcriptomic characteristics of 133 human and 66 mouse samples including five human kidney diseases and five mouse models, validating expression patterns of a central node by immunohistochemistry.
Findings:
Principal component analysis controlled for mouse background, revealed that gene expression changes in glomeruli from humans with DKD are more similar to those of diabetic mice than they are to other human glomerular diseases. This similarity enabled the construction of a discriminatory classifier that distinguishes diabetic glomeruli from other glomerular phenotypes regardless of their species of origin. To identify where the commonality between mice and humans with diabetes lies, networks of maximally perturbed protein interactions were examined, identifying a central role for the epidermal growth factor receptor (EGFR). By immunohistochemical staining, we found EGFR to be approximately doubled in its glomerular expression in both humans and mice.
Interpretation:
These findings indicate that diabetic mouse models do mimic some of the features of human kidney disease, at least with respect to their glomerular transcriptomic signatures, and they identify EGFR as being a central player in this inter-species overlap.
Insights
Diabetic kidney disease mouse models show similar glomerular gene expression to humans, identifying the epidermal growth factor receptor (EGFR) as a key shared factor. This validates mouse models for studying human diabetic kidney disease.
Area of Science:
- Nephrology
- Genomics
- Translational Medicine
Background:
- Therapeutic development for human diseases is hindered by uncertainties in animal model similarity.
- Diabetic kidney disease (DKD) is a leading cause of end-stage kidney disease, necessitating better models.
- The species-specificity versus disease-specificity of transcriptional profiles in DKD requires investigation.
Purpose of the Study:
- To determine if transcriptional profiles in diabetic kidney disease are primarily disease-specific or species-specific.
- To assess the validity of mouse models for studying human diabetic kidney disease.
- To identify molecular commonalities between human and mouse DKD.
Main Methods:
- Meta-comparison of glomerular transcriptomic data from 133 human and 66 mouse samples.
- Inclusion of five human kidney diseases and five corresponding mouse models.
- Validation of key gene expression patterns using immunohistochemistry.
Main Results:
- Principal component analysis revealed glomerular gene expression in human DKD is more similar to diabetic mice than to other human glomerular diseases.
- A classifier was built to distinguish diabetic glomeruli from other glomerular phenotypes across species.
- The epidermal growth factor receptor (EGFR) was identified as a central node in the shared molecular pathways, with doubled expression in both human and mouse DKD glomeruli.
Conclusions:
- Diabetic mouse models partially mimic human kidney disease features, particularly in glomerular transcriptomic signatures.
- The epidermal growth factor receptor (EGFR) plays a central role in the shared molecular mechanisms between human and mouse DKD.
- These findings support the use of mouse models for understanding human diabetic kidney disease.
