Abstract
Extracellular vesicles (EVs) have been isolated in different body fluids, including urine. The cargo of urinary EVs is composed of nucleic acids and proteins reflecting the physiological and possibly pathophysiological state of cells lining the nephron and the urinary tract. Urinary EVs have been confirmed to contain low amounts of various types of RNA that play a role in intercellular communication by transferring genetic information. This communication through EV RNAs includes both continuation of normal physiological processes and conditioning in disease mechanisms. Although proteins included in urinary EVs represent only 3% of the whole-urine proteome, urinary EVs can influence cells in the renal epithelia not only by delivering RNA cargo, but also by delivering a wide range of proteins. Since urine is a readily available biofluid, the discovery of EVs has opened a new field of biomarker research. The potential use of urinary EV RNAs and proteins as diagnostic biomarkers for various kidney and urologic diseases is currently being explored. Here, we review recent studies that deal in identifying biomarker candidates for human kidney and urologic diseases using urinary EVs and might help to understand the pathophysiology.
Highlights
The discovery of extracellular vesicles (EVs) in human plasma dates back to 1967, when this subcellular fraction was identified by electron microscopy by Wolf and was shown to consist of small vesicles, with a diameter between 20 and 50 nm, originating from platelets and termed “platelet dust”
In 1996, over a decade after the detection of exosomes in reticulocytes, other investigators [4] established that major histocompatibility complex (MHC)-II-enriched multivesicular endosomes in B lymphocytes fused with the plasma membrane to release exosomes bearing MHC-II, and these exosomes were able to present the peptide–MHC-II complex that activated the T cell response
Several promising early biomarkers of acute kidney injury have been identified in urine, including neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18) and kidney injury molecule-1 (KIM-1), that are in advanced stages of validation while despite the increasing number of studies on the EVs, urinary EV biomarker discovery remains in its infancy for insufficient number of patients involved in above mentioned studies
Summary
The discovery of extracellular vesicles (EVs) in human plasma dates back to 1967, when this subcellular fraction was identified by electron microscopy by Wolf and was shown to consist of small vesicles, with a diameter between 20 and 50 nm, originating from platelets and termed “platelet dust”. All cell types liberate EVs as well as tumour cells [42], antigen presenting cells [4,43], T cells [44], stem cells [11] and epithelial cells [45] They are present in the plasma and other body fluids, including breast milk, semen, saliva, urine and sputum. They have a key role in the regulation of normal physiological processes, such as stem cell maintenance [8], tissue repair [46], immune surveillance [4] and blood coagulation [47], and in the pathology of several diseases
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