Extracellular vesicles in diagnosis and therapy of kidney diseases.

Extracellular vesicles (EV) are endogenously produced, membrane-bound vesicles that contain various molecules. Depending on their size and origins, EVs are classified into apoptotic bodies, microvesicles, and exosomes. A fundamental function of EVs is to mediate intercellular communication. In kidneys, recent research has begun to suggest a role of EVs, especially exosomes, in cell-cell communication by transferring proteins, mRNAs, and microRNAs to recipient cells as nanovectors. EVs may mediate the cross talk between various cell types within kidneys for the maintenance of tissue homeostasis. They may also mediate the cross talk between kidneys and other organs under physiological and pathological conditions. EVs have been implicated in the pathogenesis of both acute kidney injury and chronic kidney diseases, including renal fibrosis, end-stage renal disease, glomerular diseases, and diabetic nephropathy. The release of EVs with specific molecular contents into urine and plasma may be useful biomarkers for kidney disease. In addition, EVs produced by cultured cells may have therapeutic effects for these diseases. However, the role of EVs in kidney diseases is largely unclear, and the mechanism underlying EV production and secretion remains elusive. In this review, we introduce the basics of EVs and then analyze the present information about the involvement, diagnostic value, and therapeutic potential of EVs in major kidney diseases.

[1]  Pieter Vader,et al.  Extracellular vesicles for drug delivery. , 2016, Advanced drug delivery reviews.

[2]  Bo Wang,et al.  Mesenchymal Stem Cells Deliver Exogenous MicroRNA-let7c via Exosomes to Attenuate Renal Fibrosis. , 2016, Molecular therapy : the journal of the American Society of Gene Therapy.

[3]  M. Janowski,et al.  Extracellular Vesicles in Physiology, Pathology, and Therapy of the Immune and Central Nervous System, with Focus on Extracellular Vesicles Derived from Mesenchymal Stem Cells as Therapeutic Tools , 2016, Front. Cell. Neurosci..

[4]  D. Meckes,et al.  ExtraPEG: A Polyethylene Glycol-Based Method for Enrichment of Extracellular Vesicles , 2016, Scientific Reports.

[5]  Hong-Jian Zhu,et al.  Extracellular vesicle isolation and characterization: toward clinical application. , 2016, The Journal of clinical investigation.

[6]  Clotilde Théry,et al.  Communication by Extracellular Vesicles: Where We Are and Where We Need to Go , 2016, Cell.

[7]  X. Niu,et al.  Exosomes secreted by human urine-derived stem cells could prevent kidney complications from type I diabetes in rats , 2016, Stem Cell Research & Therapy.

[8]  Charlotte Lawson,et al.  Microvesicles and exosomes: new players in metabolic and cardiovascular disease. , 2016, The Journal of endocrinology.

[9]  Nunzio Iraci,et al.  Focus on Extracellular Vesicles: Physiological Role and Signalling Properties of Extracellular Membrane Vesicles , 2016, International journal of molecular sciences.

[10]  Elmar L. Gool,et al.  Recent developments in the nomenclature, presence, isolation, detection and clinical impact of extracellular vesicles , 2016, Journal of thrombosis and haemostasis : JTH.

[11]  T. Le,et al.  Extracellular Vesicles in Renal Diseases: More than Novel Biomarkers? , 2016, Journal of the American Society of Nephrology : JASN.

[12]  J. Klein,et al.  Increased expression of lysosome membrane protein 2 in glomeruli of patients with idiopathic membranous nephropathy , 2015, Proteomics.

[13]  Mirja Krause,et al.  Exosomes as renal inductive signals in health and disease, and their application as diagnostic markers and therapeutic agents , 2015, Front. Cell Dev. Biol..

[14]  S. Dimmeler,et al.  Rab7a and Rab27b control secretion of endothelial microRNA through extracellular vesicles , 2015, FEBS letters.

[15]  D. Allan,et al.  Human endothelial colony-forming cells protect against acute kidney injury: role of exosomes. , 2015, The American journal of pathology.

[16]  Leonora Balaj,et al.  Extracellular Vesicles: Composition, Biological Relevance, and Methods of Study. , 2015, Bioscience.

[17]  Roman M. Ženka,et al.  Identification of Biomarkers for PKD1 Using Urinary Exosomes. , 2015, Journal of the American Society of Nephrology : JASN.

[18]  P. Provero,et al.  AKI Recovery Induced by Mesenchymal Stromal Cell-Derived Extracellular Vesicles Carrying MicroRNAs. , 2015, Journal of the American Society of Nephrology : JASN.

[19]  G. Camussi,et al.  Endothelial progenitor cell-derived extracellular vesicles protect from complement-mediated mesangial injury in experimental anti-Thy1.1 glomerulonephritis. , 2015, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[20]  A. Brisson,et al.  High-speed centrifugation induces aggregation of extracellular vesicles , 2015, Journal of extracellular vesicles.

[21]  B. Bussolati,et al.  Extracellular vesicles in the urine: markers and mediators of tissue damage and regeneration , 2014, Clinical kidney journal.

[22]  G. Camussi,et al.  Human liver stem cells and derived extracellular vesicles improve recovery in a murine model of acute kidney injury , 2014, Stem Cell Research & Therapy.

[23]  C. Théry,et al.  Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. , 2014, Annual review of cell and developmental biology.

[24]  R. Felder,et al.  Exosomal transfer from human renal proximal tubule cells to distal tubule and collecting duct cells. , 2014, Clinical biochemistry.

[25]  Yuh-Feng Lin,et al.  Exosomal ATF3 RNA Attenuates Pro‐Inflammatory Gene MCP‐1 Transcription in Renal Ischemia‐Reperfusion , 2014, Journal of cellular physiology.

[26]  R. Touyz,et al.  Urinary podocyte microparticles identify prealbuminuric diabetic glomerular injury. , 2014, Journal of the American Society of Nephrology : JASN.

[27]  K. Ma,et al.  CD2AP mRNA in urinary exosome as biomarker of kidney disease. , 2014, Clinica chimica acta; international journal of clinical chemistry.

[28]  Gloria Alvarez-Llamas,et al.  Diabetic nephropathy induces changes in the proteome of human urinary exosomes as revealed by label-free comparative analysis. , 2014, Journal of proteomics.

[29]  C. Suazo,et al.  Urinary exosomes as a source of kidney dysfunction biomarker in renal transplantation. , 2013, Transplantation proceedings.

[30]  D. Cimino,et al.  Urinary Exosomal MicroRNAs in Incipient Diabetic Nephropathy , 2013, PloS one.

[31]  J. Inal,et al.  Blood/plasma secretome and microvesicles. , 2013, Biochimica et biophysica acta.

[32]  L. Lv,et al.  MicroRNA-29c in urinary exosome/microvesicle as a biomarker of renal fibrosis. , 2013, American journal of physiology. Renal physiology.

[33]  G. Remuzzi,et al.  Pathophysiology of proteinuria and its value as an outcome measure in chronic kidney disease , 2013, British journal of clinical pharmacology.

[34]  M. Sánchez-Niño,et al.  Osteoprotegerin in Exosome-Like Vesicles from Human Cultured Tubular Cells and Urine , 2013, PloS one.

[35]  R. Star,et al.  Urinary exosomal Wilms' tumor-1 as a potential biomarker for podocyte injury. , 2013, American journal of physiology. Renal physiology.

[36]  F. Magni,et al.  Urinary exosomes and diabetic nephropathy: a proteomic approach. , 2013, Molecular bioSystems.

[37]  E. Bhatia,et al.  Wilm's Tumor-1 Protein Levels in Urinary Exosomes from Diabetic Patients with or without Proteinuria , 2013, PloS one.

[38]  Vincent H. Gattone,et al.  TGF-β1-containing exosomes from injured epithelial cells activate fibroblasts to initiate tissue regenerative responses and fibrosis. , 2013, Journal of the American Society of Nephrology : JASN.

[39]  Lynne T. Bemis,et al.  Standardization of sample collection, isolation and analysis methods in extracellular vesicle research , 2013, Journal of extracellular vesicles.

[40]  M. Logozzi,et al.  Exosomes: the ideal nanovectors for biodelivery , 2013, Biological chemistry.

[41]  Wei Zhu,et al.  Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro , 2013, Stem Cell Research & Therapy.

[42]  Larissa Ivanova,et al.  Urinary biomarkers in obstructive nephropathy. , 2012, Clinical journal of the American Society of Nephrology : CJASN.

[43]  M. Simões,et al.  Bone Marrow-Derived Mesenchymal Stem Cells Repaired but Did Not Prevent Gentamicin-Induced Acute Kidney Injury through Paracrine Effects in Rats , 2012, PloS one.

[44]  Paul Harrison,et al.  Classification, Functions, and Clinical Relevance of Extracellular Vesicles , 2012, Pharmacological Reviews.

[45]  G. London,et al.  Predictive value of circulating endothelial microparticles for cardiovascular mortality in end-stage renal failure: a pilot study. , 2012, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[46]  G. Camussi,et al.  Microvesicles Derived from Mesenchymal Stem Cells Enhance Survival in a Lethal Model of Acute Kidney Injury , 2012, PloS one.

[47]  V. Miller,et al.  Methodology for isolation, identification and characterization of microvesicles in peripheral blood. , 2012, Journal of immunological methods.

[48]  Suresh Mathivanan,et al.  ExoCarta 2012: database of exosomal proteins, RNA and lipids , 2011, Nucleic Acids Res..

[49]  H. Cheong,et al.  Urinary exosomal WT1 in childhood nephrotic syndrome , 2012, Pediatric Nephrology.

[50]  J. Dear,et al.  Exosomal transmission of functional aquaporin 2 in kidney cortical collecting duct cells , 2011, The Journal of physiology.

[51]  Scott D Emr,et al.  The ESCRT pathway. , 2011, Developmental cell.

[52]  D. Hwang,et al.  Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy , 2011, Proteomics.

[53]  G. Camussi,et al.  Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia-reperfusion-induced acute and chronic kidney injury. , 2011, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[54]  M. Wood,et al.  Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes , 2011, Nature Biotechnology.

[55]  Luigi Biancone,et al.  Exosomes/microvesicles as a mechanism of cell-to-cell communication. , 2010, Kidney international.

[56]  Johan Skog,et al.  Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease. , 2010, Kidney International.

[57]  R. Selgas,et al.  Effect of different dialysis modalities on microinflammatory status and endothelial damage. , 2010, Clinical journal of the American Society of Nephrology : CJASN.

[58]  Tian Sheng Chen,et al.  Mesenchymal stem cell secretes microparticles enriched in pre-microRNAs , 2009, Nucleic acids research.

[59]  K. Uchida,et al.  Decreased abundance of urinary exosomal aquaporin-1 in renal ischemia-reperfusion injury. , 2009, American journal of physiology. Renal physiology.

[60]  H. Ulger,et al.  The relationship between circulating endothelial microparticles and arterial stiffness and atherosclerosis in children with chronic kidney disease. , 2009, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[61]  Alessandro Busca,et al.  Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. , 2009, Journal of the American Society of Nephrology : JASN.

[62]  N. LaRusso,et al.  Characterization of PKD protein-positive exosome-like vesicles. , 2009, Journal of the American Society of Nephrology : JASN.

[63]  Trairak Pisitkun,et al.  Large-scale proteomics and phosphoproteomics of urinary exosomes. , 2009, Journal of the American Society of Nephrology : JASN.

[64]  G. Illei,et al.  Urinary exosomal transcription factors, a new class of biomarkers for renal disease. , 2008, Kidney international.

[65]  H. Cheong,et al.  Reduced urinary excretion of thiazide-sensitive Na-Cl cotransporter in Gitelman syndrome: preliminary data. , 2007, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[66]  R. Star,et al.  Exosomal Fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury. , 2006, Kidney international.

[67]  V. Faure,et al.  Elevation of circulating endothelial microparticles in patients with chronic renal failure , 2006, Journal of thrombosis and haemostasis : JTH.

[68]  Chantal M Boulanger,et al.  Circulating endothelial microparticles are associated with vascular dysfunction in patients with end-stage renal failure. , 2005, Journal of the American Society of Nephrology : JASN.

[69]  M. Hristov,et al.  Apoptotic bodies from endothelial cells enhance the number and initiate the differentiation of human endothelial progenitor cells in vitro. , 2004, Blood.

[70]  Rong-Fong Shen,et al.  Identification and proteomic profiling of exosomes in human urine. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[71]  J. Verbavatz,et al.  Localization of the CHIP28 water channel in reabsorptive segments of the rat male reproductive tract. , 1993, European journal of cell biology.