Farzamikia Negin, Hejazian Seyyedeh Mina, Mostafavi Soroush, Baradaran Behzad, Zununi Vahed Sepideh, Ardalan Mohammadreza
Kidney Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Bioimpacts. 2024;14(3):29981. doi: 10.34172/bi.2023.29981. Epub 2023 Oct 31.
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.
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.
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 ( = 0.002, = 0.06) and healthy controls, respectively ( = 0.020, = 0.001).
Different levels of the studied proteins in uEVs may indicate podocyte injury and represent a direct association with the pathology of IgAN and MGN.
尿细胞外囊泡(uEVs)可被视为肾脏疾病的生物标志物。源自足细胞的囊泡可能反映不同肾小球疾病中的足细胞损伤。IgA肾病(IgAN)是肾小球肾炎(GN)最常见的形式之一,其特征为蛋白尿和血尿。本研究旨在分析IgAN患者的uEVs,以在蛋白质水平了解该疾病的病理生理过程。
本研究纳入了GN患者[经活检证实的IgAN(n = 16)和膜性肾小球肾炎(MGN,n = 16)]以及健康对照者(n = 16)。提取、表征并分析uEVs,通过蛋白质印迹分析评估IgAN候选标志物的蛋白质水平,包括血管紧张素原前体、氨肽酶N和铜蓝蛋白。
与健康对照者相比,GN患者的混合尿液样本中观察到足细胞和与囊泡相关的蛋白质水平均更高。在IgAN患者中,与MGN患者相比,血管紧张素原的uEV - 蛋白质水平在统计学上较低,而铜蓝蛋白水平则显著更高(P = 0.002,P = 0.06),与健康对照者相比也分别显著更高(P = 0.020,P = 0.001)。
uEVs中所研究蛋白质的不同水平可能表明足细胞损伤,并与IgAN和MGN的病理直接相关。