Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy

Moon, Pyong Gon; Lee, Jeong-Eun; You, Sungyong; Kim, Taek Kyun; Cho, Ji Hoon; Kim, In San; Kwon, Tae Hwan; Kim, Chan Duck; Park, Sun Hee; Hwang, Daehee; Kim, Yong Lim; Baek, Moon Chang

doi:10.1002/pmic.201000443

Cited by 219 publications

(176 citation statements)

References 61 publications

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“…These candidates are aminopeptidase N, vasorin precursor, a-1-antitrypsin, and ceruloplasmin. 84 Validation studies are needed, especially to define the predictive role of these potential novel markers. It would also be important to determine whether these proteins within exosomes have causal or protective roles in disease.…”

Section: Glomerular Diseasementioning

confidence: 99%

Extracellular Vesicles in Renal Diseases

Erdbrügger

2016

Journal of the American Society of Nephrology

168

175

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Extracellular vesicles from the urine and circulation have gained significant interest as potential diagnostic biomarkers in renal diseases. Urinary extracellular vesicles contain proteins from all sections of the nephron, whereas most studied circulating extracellular vesicles are derived from platelets, immune cells, and the endothelium. In addition to their diagnostic role as markers of kidney and vascular damage, extracellular vesicles may have functional significance in renal health and disease by facilitating communication between cells and protecting against kidney injury and bacterial infection in the urinary tract. However, the current understanding of extracellular vesicles has derived mostly from studies with very small numbers of patients or in vitro data. Moreover, accurate assessment of these vesicles remains a challenge, in part because of a lack of consensus in the methodologies to measure extracellular vesicles and the inability of most techniques to capture the entire size range of these vesicles. However, newer techniques and standardized protocols to improve the detection of extracellular vesicles are in development. A clearer understanding of the composition and biology of extracellular vesicles will provide insights into their pathophysiologic, diagnostic, and therapeutic roles.

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Section: Glomerular Diseasementioning

confidence: 99%

Extracellular Vesicles in Renal Diseases

Erdbrügger

2016

Journal of the American Society of Nephrology

168

175

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“…14 Accordingly, several proteomic studies on urinary exosomes have been performed to identify biomarkers predictive of urinary track diseases, both in experimental and clinical settings. 7,13,[15][16][17][18] For an exhaustive review see Moon et al 19 However no proteomic study of urinary exosomes has been yet accomplished in RCC. Therefore, we performed MS profiling and antibody-based validation and quantification of differential proteins in urinary exosomes from a RCC patient cohort in order to search for a potential tumor marker.…”

Section: Introductionmentioning

confidence: 99%

Differential protein profiling of renal cell carcinoma urinary exosomes

et al. 2013

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aRenal cell carcinoma (RCC) accounts for about 3% of all human malignancies and its incidence is increasing. There are no standard biomarkers currently used in the clinical management of patients with renal cell carcinoma. A promising strategy for new biomarker detection is comparative proteomics of urinary exosomes (UE), nanovesicles released by every epithelial cell facing the urinary space, enriched in renal proteins and excluding high-abundance plasmatic proteins, such as albumin. Aim of the work is to establish the protein profile of exosomes isolated from urines of RCC patient compared with control subjects. We enrolled 29 clear cell RCC patients and 23 control healthy subjects (CTRL), age and sex-matched, for urine collection and vesicle isolation by differential centrifugation. Such vesicles were morphologically and biochemically characterized and proved to share exosome properties.Proteomic analysis, performed on 9 urinary exosome (UE) pooled samples by gel based digestion followed by LC-MS/MS, led to the identification of 261 proteins from CTRL subject UE and 186 from RCC patient UE, and demonstrated that most of the identified proteins are membrane associated or cytoplasmic. Moreover, about a half of identified proteins are not shared between RCC and control UE.Starting from these observations, and from the literature, we selected a panel of 10 proteins, whose UE differential content was subjected to immunoblotting validation. Results show for the first time that RCC UE protein content is substantially and reproducibly different from control UE, and that these differences may provide clues for new RCC biomarker discovery.

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“…Over the last few years, urinary proteomic profile analysis of IgAN patients suggested that the excreted polypeptides include disease-specific patterns (27)(28)(29). However, these different proteomic strategies, complementary to each other, were restricted to the limited mass range of ion signal m/z,10,000 (27,28) and the tryptic peptides (29).…”

Section: Discussionmentioning

confidence: 99%

Association of Urinary Laminin G-Like 3 and Free K Light Chains with Disease Activity and Histological Injury in IgA Nephropathy

Rocchetti

Papale

d'Apollo

et al. 2013

Clinical Journal of the American Society of Nephrology

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Summary Background and objectives IgA nephropathy has variable clinical presentation and progression. Its definitive diagnosis and prognosis require renal biopsy. The identification of new biomarkers allowing noninvasive diagnosis and monitoring of disease activity would be advantageous. This study analyzed the urine proteome of IgA nephropathy patients at an early stage of disease. Design, setting, participants, & measurements Urine from 49 IgA nephropathy patients, 42 CKD patients, and 40 healthy individuals was analyzed by surface-enhanced laser desorption/ionization time of flight/mass spectrometry. Differentially excreted proteins were identified by matrix-enhanced laser desorption/ionization time of flight/mass spectrometry, confirmed by immunologic methods, and validated in an independent set of patients (14 IgA nephropathy and 24 CKD). All patients were recruited at the Division of Nephrology of the University of Foggia from January of 2005 to March of 2007. Results Two proteins, with 21,598 and 23,458 m/z, were significantly decreased in IgA nephropathy and identified as Perlecan laminin G-like 3 peptide and Ig κ light chains, respectively. Western blot analysis confirmed the lower urinary excretion of laminin G-like 3 in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunonephelometry analysis confirmed the lower urinary excretion of free κ light chains in IgA nephropathy patients compared with CKD patients and healthy individuals. Immunohistochemistry analysis justified the urinary excretion profile of such proteins in IgA nephropathy. Finally, urinary free κ light chains and laminin G-like 3 concentration inversely correlated with severity of clinical and histologic features of our IgA nephropathy cohort. Conclusions Laminin G-like 3 and free κ light chains can contribute to the noninvasive assessment of IgA nephropathy disease activity.

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Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy

Cited by 219 publications

References 61 publications

Extracellular Vesicles in Renal Diseases

Extracellular Vesicles in Renal Diseases

Differential protein profiling of renal cell carcinoma urinary exosomes

Association of Urinary Laminin G-Like 3 and Free K Light Chains with Disease Activity and Histological Injury in IgA Nephropathy

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