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Updated: Sep 24, 2025
Comparative Proteomic Analysis of Whole Kidney, Medulla, and Cortical Tubules in Diabetic Pathogenesis of Kidney Injury in Mice
Published on: May 2, 2025
Glucagon-Like Peptide 1 Receptor Agonist Improves Renal Tubular Damage in Mice with Diabetic Kidney Disease
Ran Li1, Dunmin She2, Zhengqin Ye1
1Department of Endocrinology and Metabolism, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, People's Republic of China.
Purpose:
This study aims to investigate the renal protective effect of glucagon-like peptide 1 receptor agonist (GLP-1RA) on improving renal tubular damage in diabetic kidney disease (DKD) and to explore the potential mechanism of GLP-1RA on renal tubular protection.
Methods:
Long-acting GLP-1RA was used to treat DKD mice for 12 weeks. The label-free quantitative proteomic analysis of renal proteins was conducted to explore the differentially expressed proteins (DEPs) in the renal tissues of the control, DKD and GLP-1RA groups. The DEPs and markers of renal tubular injury were verified by qPCR in vivo and in vitro. The expression of glucagon-likepeptide-1 receptor (GLP-1R) in renal tubules was determined by immunofluorescence staining.
Results:
GLP-1RA treatment significantly improved the tubular damages in kidney tissues of DKD mice and mTEC cells stimulated by high glucose (HG). Proteomics analysis revealed that 30 proteins in kidney tissue were differentially expressed among three groups. Seminal vesicle secretory protein 6 (SVS6) was the most differentially expressed protein in kidney tissues among three groups of mice. The expression changes of Svs6 mRNA in vitro and in vivo detected by qPCR were consistent with the results of proteomic analysis. Furthermore, reduction of Svs6 expression by SVS6 siRNA could attenuate HG-stimulated tubular injury in mTEC cells. Immunofluorescence staining also found that GLP-1R was widely expressed in renal tubules in vitro and in vivo.
Conclusion:
GLP-1RA significantly improved renal tubular damage in DKD mice. SVS6 may be a potential therapeutic target for GLP-1RA in the treatment of DKD.
Insights
Glucagon-like peptide 1 receptor agonist (GLP-1RA) treatment improved kidney damage in diabetic kidney disease (DKD) mice. Seminal vesicle secretory protein 6 (SVS6) was identified as a potential therapeutic target for DKD treatment.
Area of Science:
- Nephrology
- Endocrinology
- Molecular Biology
Background:
- Diabetic kidney disease (DKD) is a major complication of diabetes, characterized by progressive renal tubular damage.
- Glucagon-like peptide 1 receptor agonists (GLP-1RAs) are increasingly used for diabetes management and have shown potential renoprotective effects.
Purpose of the Study:
- To investigate the renal protective effects of GLP-1RA in DKD.
- To explore the underlying molecular mechanisms, focusing on renal tubular protection.
Main Methods:
- DKD mice were treated with a long-acting GLP-1RA for 12 weeks.
- Label-free quantitative proteomics identified differentially expressed proteins (DEPs) in renal tissues.
- Quantitative PCR (qPCR) and immunofluorescence validated protein and receptor expression in vivo and in vitro.
- siRNA was used to reduce Seminal vesicle secretory protein 6 (SVS6) expression.
Main Results:
- GLP-1RA treatment significantly ameliorated tubular damage in DKD mice and high glucose-stimulated renal tubular cells.
- Proteomic analysis revealed 30 DEPs, with SVS6 being the most significantly altered.
- Svs6 mRNA expression changes correlated with proteomic findings.
- Reduced SVS6 expression attenuated high glucose-induced tubular injury.
- Glucagon-like peptide-1 receptor (GLP-1R) was widely expressed in renal tubules.
Conclusions:
- GLP-1RA demonstrates significant renal protective effects in DKD, improving tubular damage.
- SVS6 emerges as a potential therapeutic target for GLP-1RA in DKD treatment.
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