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Urinary extracellular vesicles as reservoirs of altered proteins during the pathogenesis of polycystic kidney disease
Author(s) -
Pocsfalvi Gabriella,
Raj Delfin A. A.,
Fiume Immacolata,
Vilasi Annalisa,
Trepiccione Francesco,
Capasso Giovambattista
Publication year - 2015
Publication title -
proteomics – clinical applications
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.948
H-Index - 54
eISSN - 1862-8354
pISSN - 1862-8346
DOI - 10.1002/prca.201400199
Subject(s) - pathogenesis , extracellular vesicles , vesicle , polycystic kidney , polycystic kidney disease , urinary system , disease , extracellular , kidney , medicine , chemistry , pathology , endocrinology , biology , microbiology and biotechnology , biochemistry , membrane
Purpose Recent findings indicate that urinary extracellular vesicles (EVs) might reflect the pathophysiological state of urinary system; and that EVs‐induced ciliary signaling is a possible mechanism of intercellular communication within the tract. Here, we aimed to analyze the protein expression of urinary EVs during autosomal dominant polycystic kidney disease (ADPKD). Experimental design EVs were isolated from pooled urine samples of healthy control and ADPKD patients at two different stages of the disease and under tolvaptan treatment using the double‐cushion ultracentrifugation method. Proteins were identified and quantified by iTRAQ and multidimensional protein identification technology (MudPIT)‐based quantitative proteomics. Results Quantitative analyses identified 83 differentially expressed EV proteins. Many of these have apical membrane origin and are involved in signal transduction pathways of primary cilia, Ca 2+ ‐activated signaling, cell‐cycle regulation, and cell differentiation. Conclusions and clinical relevance The reduced AQP‐2 and the increased APO‐A1 levels observed in all ADPKD‐affected groups may reflects the impaired renal concentrating capability of these patients and correlated with estimated glomerular filtration rate decline. The levels of some upregulated proteins involved in Ca 2+ ‐activated signaling declined upon tolvaptan treatment. The results obtained suggest that the quantitative proteomics of urinary EVs might be useful to monitor proteins difficult to access noninvasively, and thus advance our understanding of urinary tract physiology and pathology.