Abstract: SA-PO0305
SIRPα Neutralization Reverses Kidney Lipid Metabolism Defects, Improving Kidney Function Despite Hyperglycemia in Type 1 Diabetes
Session Information
- Diabetic Kidney Disease: Basic and Translational Science Advances - 2
November 08, 2025 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Wu, Jiao, Baylor College of Medicine, Houston, Texas, United States
- Hu, Zhaoyong, Baylor College of Medicine, Houston, Texas, United States
- Thomas, Sandhya S., Baylor College of Medicine, Houston, Texas, United States
Background
Mechanisms responsible for skeletal muscle kidney crosstalk have not been defined. We have determined that SIRPα, a circulating mediator, impairs intracellular insulin-mediated functions. To determine insulin-independent effects on kidney fatty acid oxidation, a model of significant hyperglycemia was utilized, streptozotocin (STZ), an insulinopenic model.
Methods
To elucidate the impact of myokine SIRPα on diabetic kidney disease (DKD), a model of significant hyperglycemia was utilized, streptozotocin (STZ), an insulinopenic model. Three groups of mice (fl/fl, mSIRPα-/-, or anti-SIRPα monoclonal antibody (mAb)-treated fl/fl mice) were treated with STZ to induce significant hyperglycemia. Methods of evaluation include qPCR, immunohistochemistry, with sirius red staining and serum measurements.
Results
Suppressing SIRPα in skeletal muscles or treatment with anti-SIRPα monoclonal antibodies in STZ-treated mice, mitigated cachexia, proteinuria, polyuria, when compared to flox STZ-treated mice. Next, serum and kidney triglyceride, total cholesterol, lipid deposition, glomerular size, and importantly serum creatinine were found to be significantly reduced in STZ-treated mSIRPα-/- or anti-SIRPα-fl/fl mice. Additionally, STZ was found to suppress renal FAO transcripts with upregulation of genes encoding fibrosis in STZ-treated fl/fl mice vs. their respective control mice. In fact, FAO was found to be improved in mSIRPα-/-, or anti-SIRPα mAb-treated mice when comparing with fl/fl mice after STZ treatment.
Conclusion
In conclusion, blocking SIRPα improved kidney fatty acid metabolism and prevented diabetic kidney damage. Therefore, SIRPα serves as a novel biomarker and therapeutic target in diabetic kidney disease.
Funding
- Veterans Affairs Support