Perturbations in the Urinary Exosome in Transplant Rejection

Sigdel, Tara K.; Ng, Yolanda W.; Lee, Sang-Ho; Nicora, Carrie; Qian, Weijun; Smith, Richard; Camp, David G.; Sarwal, Minnie M.

doi:10.3389/fmed.2014.00057

Cited by 47 publications

(51 citation statements)

References 34 publications

(48 reference statements)

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“…In addition to this, SERPINA1, A2M, APOA1, APOA2, CA1, CD5L, DPEP1, SLC2A1, RAB27B and TACSTD2 were among the proteins that significantly differentiated hernia from bladder cancer patients. Both cocktails of changing proteins are similar to the group of proteins abundant in patients with kidney transplant AR analyzed by Sigdel et al [71]. Remarkably, the levels of TACSTD2 determined by LC-MRM-MS were 6.5-fold higher in bladder cancer urinary vesicles than in hernia patients.…”

Section: Urinary Vesicles and Bladder Cancersupporting

confidence: 60%

“…Indeed, urinary exosomes could also be useful to evaluate patients after kidney transplantation as shown by Sigdel et al [71]. They analyzed by mass spectroscopy-based quantitative proteomics urinary exosomes from kidney transplant patients with and without acute rejection (AR).…”

Section: Urinary Vesicles and Nephritic Conditionsmentioning

confidence: 99%

“…A2M Urine Kidney transplantation [71] Urine Bladder cancer, hernia [73] APOA2 Urine Kidney transplantation [71] Urine Bladder cancer, hernia [73] CD5L Urine Kidney transplantation [71] Urine Bladder cancer, hernia [73] CD24 Ascites Ovarian cancer [59,61] Ascites Breast cancer [61] CD41a Plasma Gastric cancer [32] Blood Prostate cancer [31] CD45 Plasma Autoimmune diseases [49] Plasma Autoimmune diseases [50] CD63 Plasma Melanoma [38] Plasma Colon cancer [37] Serum Ovarian cancer [7] EGFRvIII Serum Ovarian cancer [7] EGFRvIII Serum Glioblastoma [41] EpCAM Plasma Colon cancer [37] Plasma Lung cancer [35] Serum Ovarian cancer [39] Ascites Ovarian cancer [59,61] Ascites Breast cancer [61] FGA Urine Kidney transplantation [71] Urine Bladder cancer (grade) [73] FGB Urine Kidney transplantation [71] Urine Bladder cancer (grade) [73] miR-21 Serum Glioblastoma [41] Serum Laryngeal cancer [44] Serum Esophageal cancer [43] Plasma Lung cancer [35] Serum Ovarian cancer [39] Serum Liver disease (HepB, HCC) ITGB1, two proteins involved in migration/invasion [83]. The study pointed out that these two proteins play a relevant role in changing non-cancerous neighboring cells.…”

Section: Serummentioning

confidence: 99%

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Cell-derived extracellular vesicles as a platform to identify low-invasive disease biomarkers

González

Falcón‐Pérez

2015

Expert Review of Molecular Diagnostics

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Biomarkers are of great importance for prediction, diagnosis and monitoring the progression and therapeutic success of a disease. Whole body fluids, such as blood or urine, constitute the main desired biological source to identify these markers, mostly due to the minimally invasive procedures used to collect them. An additional benefit of studying these biological fluids that has been demonstrated by many different groups is that they contain cell-released extracellular vesicles, carrying a cargo of lipids, proteins and nucleic acids that reflects cell/tissue origin and, remarkably, cellular status. In this review, the information obtained from the characterization of this body fluid compartment in human samples is discussed in the context of its usefulness as diagnostic resource for several pathologies, including cancer, inflammatory, vascular and metabolic diseases. The review shows the great variety of methods used for this purpose as well as the different types of molecules that could serve as specific or common disease markers.

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Section: Urinary Vesicles and Bladder Cancersupporting

confidence: 60%

Section: Urinary Vesicles and Nephritic Conditionsmentioning

confidence: 99%

Section: Serummentioning

confidence: 99%

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Cell-derived extracellular vesicles as a platform to identify low-invasive disease biomarkers

González

Falcón‐Pérez

2015

Expert Review of Molecular Diagnostics

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“…Various protein compendia of urinary exosomes have been reported35192223242526, but the identification of their miRNA content has been limited to one sequence based study10, and three studies utilising RT-qPCR or microarray approaches that restrict the study to a specific set of known miRNAs71527. The lack of efficient methods to isolate small RNAs from vesicles has been a constraint to miRNA profiling, and there is no consensus regarding the optimal method for isolation of exosomes.…”

mentioning

confidence: 99%

Urinary Exosomes Contain MicroRNAs Capable of Paracrine Modulation of Tubular Transporters in Kidney

Gracia

Wang

et al. 2017

Sci Rep

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Exosomes derived from all nephron segments are present in human urine, where their functionality is incompletely understood. Most studies have focused on biomarker discovery rather than exosome function. Through sequencing we identified the miRNA repertoire of urinary exosomes from healthy volunteers; 276 mature miRNAs and 345 pre-miRNAs were identified (43%/7% of reads). Among the most abundant were members of the miR-10, miR-30 and let-7 families. Targets for the identified miRNAs were predicted using five different databases; genes encoding membrane transporters and their regulators were enriched, highlighting the possibility that these miRNAs could modulate key renal tubular functions in a paracrine manner. As proof of concept, cultured renal epithelial cells were exposed to urinary exosomes and cellular exosomal uptake was confirmed; thereafter, reduced levels of the potassium channel ROMK and kinases SGK1 and WNK1 were observed in a human collecting duct cell line, while SPAK was unaltered. In proximal tubular cells, mRNA levels of the amino acid transporter gene SLC38A2 were diminished and reflected in a significant decrement of its encoded protein SNAT2. Protein levels of the kinase SGK1 did not change. Thus we demonstrated a novel potential function for miRNA in urinary exosomes.Urinary exosomes are lipid membrane-bound nanovesicles released from intracellular multivesicular bodies (MVBs) 1,2 and derived from all cells in the urinary tract [3][4][5] . During the inward budding of endosomes that give origin to exosomes, proteins 2 , mRNAs 6 , microRNAs (miRNAs) 7 , noncoding RNA (ncRNA) 8 , transcription factors 9 and other biomolecules present in the cytosol can be incorporated. The lipid bi-layer of these nanovesicles provides the cargo with stable storage conditions and protects it from degradation by extracellular proteases and ribonucleases 10. Studies in other tissues have shown that once exosomes and other microvesicles are released into the extracellular environment, interactions with cells can occur by direct ligand-receptor signalling, by exosomal fusion to the target cell membrane and discharge of exosomal content directly into the cytoplasm, or via phagocytosis/macropinocytosis 11,12 . Exosomes are known to deliver biologic cargo not only to neighbouring cells but also long distance 13 . The majority of studies concerning urinary exosomes have focused on their potential as biomarkers of disease pathology and progression, including prostate and bladder cancers [14][15][16][17] , but their functional significance is now being addressed. Inter-cellular signalling by exosomes in cultured murine renal epithelial cells was demonstrated for the first time by Street et al. 18 , who suggested that collecting duct cell-derived exosomes can transfer the ability to express AQP2. Our previous studies revealed that urinary exosomes inhibit bacterial growth of both commensal and uropathogenic E. coli by inducing bacterial lysis 19 . Bruschi and colleagues demonstrated that urinary exosomes can consume ...

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“…Urine is considered a rich reservoir of exosomes744 that are readily available by relatively inexpensively and noninvasive collection. Urine exosomes are exocytosed into urine by all renal epithelial cell types45. It is believed that the urinary exosome proteome may mirror disease specific changes not only perturbations due to renal diseases but also pathophysiology changes of other organs44.…”

mentioning

confidence: 99%

Isolation and mass spectrometry analysis of urinary extraexosomal proteins

Hildonen

Skarpen

Halvorsen

et al. 2016

Sci Rep

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The aim of the present study was to develop a LC-MS/MS-based proteomic analysis method of urinary exosomal proteins that has the potential to discover disease biomarkers. In short, urinary exosomes from healthy subjects were isolated by immunocapture on magnetic beads, detected by immunofluorescence and TEM, trypsin digested directly on the beads for an accelerated time with no addition of detergents before performing an LC-MS analysis of the trypsinate. To our knowledge, this is the first proteomic analysis of proteins displayed on the outer surface of exosomes. The outer exosome proteome may contain proteins that are of higher biomarker value compared to soluble cargo protein as the proteins projecting into the extracellular milieu might be more directly involved in physiological functions of exosomes. The proteomic analysis identified 49 proteins that were considered significant; the majority is involved in carbohydrate and lipid metabolism or in immune responses. Thirty of the proteins are linked to diseases. The developed proteomic method exploiting urinary exosomes might be of great value in search for diagnostic or prognostic biomarkers of especially metabolic and immune-related diseases.

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Perturbations in the Urinary Exosome in Transplant Rejection

Cited by 47 publications

References 34 publications

Cell-derived extracellular vesicles as a platform to identify low-invasive disease biomarkers

Cell-derived extracellular vesicles as a platform to identify low-invasive disease biomarkers

Urinary Exosomes Contain MicroRNAs Capable of Paracrine Modulation of Tubular Transporters in Kidney

Isolation and mass spectrometry analysis of urinary extraexosomal proteins

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