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Abstract: TH-PO792

Single Glomerular Proteomes Connect Morphology and Function in Proteinuric Kidney Disease

Session Information

Category: Glomerular Diseases

  • 1201 Glomerular Diseases: Fibrosis and Extracellular Matrix

Author

  • Rinschen, Markus M., CECAD, Cologne, Germany
Background

Kidney diseases are frequently heterogenous and affect different glomeruli to different extents.

Methods

We use ultrasensitive sample preparation combined with quantitative targeted and untargeted proteomics of single glomeruli to unravel functional co-expression modules in glomerular populations. We analyze microdissected glomeruli of three animal models

Results

In single glomeruli from three different rodent models of sclerotic glomerular disease, we identified a coherent protein expression module consisting of extracellular matrix protein deposition (reflecting glomerular sclerosis), glomerular albumin (reflecting proteinuria) and LAMP1, a lysosomal protein. This module was associated with a loss of podocyte marker proteins while genetic ablation of LAMP1-correlated lysosomal proteases could ameliorate glomerular damage in vivo. Furthermore, proteomic analyses of individual glomeruli from patients with genetic sclerotic and non-sclerotic proteinuric diseases revealed increased abundance of lysosomal proteins, in combination with a decreased abundance of mutated gene products.

Conclusion

Single glomerular proteomes connect morphology and function in proteinuric kidney disease. Altered protein homeostasis (proteostasis) is a conserved key mechanism in proteinuric kidney diseases. Moreover, our technology can capture intra-individual variability in diseases of the kidney and other tissues at a sub-biopsy scale.

Funding

  • Government Support - Non-U.S.