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Abstract: TH-PO184

Agnostic Mass Spectrometry Proteomics Identifies Glomerular Adipocyte Enhancer Binding Protein 1 (AEBP1) as a Novel Marker of Diabetic Kidney Disease

Session Information

Category: Diabetic Kidney Disease

  • 601 Diabetic Kidney Disease: Basic

Authors

  • Madhavan, Sethu M., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Shapiro, John P., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Almaani, Salem, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Satoskar, Anjali A., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Eadon, Michael T., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • El-Achkar, Tarek M., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Dagher, Pierre C., Indiana University School of Medicine, Indianapolis, Indiana, United States
  • Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States
  • Parikh, Samir V., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Group or Team Name

  • KPMP
Background

Diabetic kidney disease (DKD) results from progressive glomerular inflammation and fibrosis frequently resulting in ESKD. Agnostic mass spectrometry (LC-MS/MS) proteomics was performed on kidney biopsies obtained from the Kidney Precision Medicine Project (KPMP) and potential biomarkers and molecular mediators of DKD were explored.

Methods

Frozen kidney biopsies with DKD (n=9) from the KPMP consortium and nephrectomy controls from OSU biorepository (n=4) were included. Biopsies were obtained from recruitment sites in the KPMP and histopathologic diagnoses were adjudicated by an expert committee in KPMP. Glomeruli and tubulointerstitium were isolated by laser capture microdissection and extracted protein was submitted for LC-MS/MS proteomics. Global normalization was performed by spectral counting. The glomerular proteome of DKD was compared to controls. Immunofluorescence microscopy and immunoperoxidase staining were performed in another cohort of DKD (n=5) from OSU biorepository. To determine specificity, proteomics comparison from other glomerular diseases (FSGS and MCD, n=13) was done.

Results

Glomerular AEBP1 was one of the most upregulated proteins in glomeruli of DKD compared to controls (4-fold, p=0.0008). AEBP1 was minimally expressed in healthy glomeruli but strongly stained by immunoperoxidase in DKD glomeruli. AEBP1 co-localized with nephrin and CD31 suggesting podocyte and endothelial expression in another cohort of diabetic glomeruli compared to controls. AEBP1 expression was similar to controls in FSGS and MCD.

Conclusion

We identified glomerular AEBP1 as a potential novel marker of DKD. AEBP1 has previously been shown to be induced by glucose, activates inflammatory mediators and associated with liver fibrosis in non-steatohepatitis. It has not been previously studied in kidney disease. Glomerular upregulation of AEBP1 in DKD and localization in podocytes and glomerular endothelial cells suggests its role in mediating glomerular inflammation and fibrosis in DKD. AEBP1 upregulation may be specific for DKD. The causal role of AEBP1 in the pathogenesis and progression of DKD will be further investigated within the KPMP consortium utilizing clinical and histology data and a multi-omic interrogation.

Funding

  • NIDDK Support