Candidate biomarkers in exosome‐like vesicles purified from rat and mouse urine samples

Conde‐Vancells, Javier; Rodríguez-Suárez, Eva; González, Esperanza; Berisa, A.; Gil, David; Embade, Nieves; Valle, Mikel; Luka, Zigmund; Elortza, Félix; Wagner, Conrad; Lu, Shelly C.; Mato, José M.; Falcón‐Pérez, Juan Manuel

doi:10.1002/prca.200900103

Cited by 120 publications

(84 citation statements)

References 31 publications

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“…46 Loss or decrease in neprilysin expression has been reported in many types of malignancies, including renal cancer. 34,47 DPEP1 and CD10 demonstrate to have a reduced content in RCC UE, compared to control ones, possibly according to the loss of the cellular specialization, as already mentioned. Finally, the levels of CAIX and CP are found significantly increased in RCC urinary exosomes: it has to be underlined that their promoters were reported to be activated by the transcriptional factor HIF-1a, known to be involved in RCC genesis.…”

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confidence: 57%

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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confidence: 57%

Differential protein profiling of renal cell carcinoma urinary exosomes

et al. 2013

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“…6,15 Therefore, further characterisations of these exosome-detected proteins under normal and pathological conditions will help to define them as biomarkers of diseases. 16 The present study was to evaluate the effectiveness of using analysis of urinary microvesicles to identify potential diagnostic markers for DKD. DPP IV is an intrinsic membrane glycoprotein, localised on glomerular visceral epithelial cells, endothelial cells, and the proximal tubule brush border.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease

Sun

Deng

Guan

et al. 2012

Diabetes and Vascular Disease Research

117

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The present study was designed to identify the changes in microvesicle-dipeptidyl peptidase-IV (DPP IV) levels in human urine and serum, and to determine whether there were correlations with the severity of diabetic kidney disease (DKD). A total of 127 patients with type 2 diabetes mellitus (T2DM) were divided into three groups according to the urinary albumin/ creatinine ratio (UACR): microalbuminuria group (n = 50); macroalbuminuria group (n = 34) and normoalbuminuria group (n = 43), and 34 age-and sex-matched non-diabetic healthy subjects were selected as controls. Microvesicle-bound DPP IV and free urinary DPP IV were separated by a filtra-centrifugation method. The total microvesicles were captured by a specific monoclonal antibody, AD-1. DPP IV activity was determined by measuring the cleavage of chromogenic free 4-nitroaniline from Gly-Pro-p-nitroanilide at 405 nm with an ELISA plate reader. DPP IV protein levels were determined by ELISA and Western blot. Our results showed that the microvesicle-bound type was the major form of DPP IV in urine; the urinary microvesicle-DPP IV excretion of each T2DM group was significantly higher compared with controls. The urinary microvesicle-DPP IV level was positively correlated with UACR in patients with T2DM. These findings suggest that the urinary level of microvesicle-bound DPP IV is associated with the severity of DKD.

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“…Interestingly, exosomes are the only known secreted cellular vesicles that originate from internal membranes. Exosomes have been found in many biological fluids, including urine (37,116,122), plasma (117), ascites (8), saliva (111), breast milk (3), brochoalveolar lavage liquid (124), and amniotic fluid (85), making them ideal candidates for diagnostic biomarkers.…”

Section: Exosomesmentioning

confidence: 99%