Abstract: FR-PO258
Calciprotein Particles Appear to Be Uniquely Present in Diabetic Kidneys
Session Information
- Diabetic Kidney Disease: Basic - 1
October 25, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 701 Diabetic Kidney Disease: Basic
Authors
- Shapiro, John P., The Ohio State University, Columbus, Ohio, United States
- Blissett, Angela R., The Ohio State University, Columbus, Ohio, United States
- Schurgers, Leon J., Universiteit Maastricht, Maastricht, Limburg, Netherlands
- Satoskar, Anjali A., The Ohio State University, Columbus, Ohio, United States
- Rovin, Brad H., The Ohio State University, Columbus, Ohio, United States
Background
Diabetes mellitus is commonly associated with diabetic kidney disease (DKD) that can progress to chronic kidney disease and end stage kidney disease. Mass spectrometry (MS) proteome analysis was performed on kidney biopsies obtained from the Kidney Precision Medicine Project (KPMP). Potential biomarkers and molecular mediators of DKD were explored.
Methods
KPMP obtained frozen kidney biopsy sections with DKD (n=11) and AKI (n=4) and normal controls from OSU biorepository (n=4) were analyzed using laser capture microdissection in combination with mass spectrometry. Spectral count global normalization was performed and the proteome of DKD was compared to AKI and controls. Immunofluorescence (IF) microscopy was performed on a cohort of OSU DKD and normal biopsies to confirm mass spectrometry findings.
Results
Analysis of MS data identified secreted phosphoprotein 24 (SPP24), Matrix gla protein (MGP), fetuin-A (AHSG) and serum amyloid P-component (APCS) as uniquely overexpressed in the glomeruli of DKD patients. All 4 proteins demonstrated IF co-localization within the mesangium and interstitial vasculature showing punctate and diffuse staining. These 4 proteins are known to bind to calciprotein particles (CPPs) which are protein decorated cores of calcium/phosphate. Using a monoclonal antibody specific to uncarboxylated MGP (ucMGP), a version of MGP associated with vascular calcification, we demonstrated similar IF staining pattern as the other proteins. Examination of electron micrographs from patients with kidney disease indicates the characteristic presence of electron dense particles only in the expanded mesangium of DKD patients. We believe the IF staining observed in the mesangium and interstitial vasculature and the electron dense particles observed ultrastructurally in DKD glomeruli are correlated and consist of SPP24, ucMGP, APCS and ASHG decorated CPPs.
Conclusion
SPP24, ucMGP, APCS and AHSG decorated CPPS are present in the mesangium and vasculature of DKD patients. Further studies are required to examine the effects of the CPPs and associated proteins in the glomeruli and vasculature of diabetic patients but they could be responsible for induction of endothelial and vascular smooth muscle inflammation and calcification.
Funding
- Other NIH Support