Negin Farzamikia
1,2 , Seyyedeh Mina Hejazian
1, Soroush Mostafavi
3, Behzad Baradaran
4, Sepideh Zununi Vahed
1* , Mohammadreza Ardalan
1* 1 Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
2 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Cardiology, Hazrat-e-Rasool General Hospital, Iran University of Medical ‎Sciences, Tehran, Iran
4 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Abstract
Introduction: Urinary extracellular vesicles (uEVs) can be considered biomarkers of kidney diseases. EVs derived from podocytes may reflect podocyte damage in different glomerular diseases. IgA nephropathy (IgAN) is one of the most common forms of glomerulonephritis (GN) characterized by proteinuria and hematuria. This study aimed to analyze the uEVs of IgAN patients to understand the pathophysiological processes of the disease at the protein level.
Methods: Patients with GN [biopsy-proven IgAN (n = 16) and membranous glomerulonephritis (MGN, n = 16)], and healthy controls (n = 16) were included in this study. The uEVs were extracted, characterized, and analyzed to evaluate the protein levels of candidate markers of IgAN, including vasorin precursor, aminopeptidase N, and ceruloplasmin by western-blot analysis.
Results: Higher levels of both podocytes and EVs-related proteins were observed in the pooled urine samples of GN patients compared to the healthy controls. In IgAN patients, uEV-protein levels of vasorin were statistically lower while levels of ceruloplasmin were significantly higher compared to MGN (P = 0.002, P = 0.06) and healthy controls, respectively (P = 0.020, P= 0.001).
Conclusion: Different levels of the studied proteins in uEVs may indicate podocyte injury and represent a direct association with the pathology of IgAN and MGN.