Proteomic analysis of the pathogenesis of proteinuria and nephrotic syndrome.

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A specialized intercellular junction between podocytes, known as the slit diaphragm, forms the essential structural framework for glomerular filtration in the kidney. In this study, we performed proteomic analysis to characterize the structure and function of slit diaphragm as a signaling complex. We found that post-translational modification orchestrates a wide spectrum of protein-protein interactions and intracellular signaling networks at slit diaphragm. These results unraveled the role of dynamics of slit diaphragm signal complex in modulating the glomerular filtration barrier function. We also performed genetic studies on Epstein and Fechtner syndromes which often develops progressive nephrotic syndrome, and found that R702 mutations display a strict genotype-phenotype correlation, and lead to the rapid deterioration of podocyte structure. Our results highlight the critical role of functional podocyte molecules in the development of Nephrotic syndrome.