Urinary extracellular vesicles: Origin, role as intercellular messengers and biomarkers; efficient sorting and potential treatment options

Abstract

Urinary extracellular vesicles (uEVs) are a heterogenous group of vesicles consisting mainly of microvesicles and exosomes that originate predominantly (99.96%) from kidney, the urinary tract epithelium and the male reproductive tract. Secreted EVs contain molecular cargo from parental cells and provide an attractive source for biomarkers, a potential readout of physiological and pathophysiological mechanisms, and events associated with the urinary system. uEVs are readily enriched and isolated from urine samples and we review 6 standard methods that allow for downstream analysis of the uEV cargo. Although the use of uEVs as a surrogate readout for physiological changes in tissue protein levels is widespread, the protein abundance in uEVs is affected significantly by mechanisms that regulate protein sorting and secretion in uEVs. Data suggest that baseline kidney tissue and uEV levels of apical membrane-associated electrolyte transport proteins are not directly related in human patients. Recent evidence indicates that EVs may contribute to physiological and pathophysiological intercellular signalling and EVs confer protection against renal ischemia-reperfusion injury. The therapeutic use of EVs as information carriers has mainly been explored in vitro and a major hurdle lies in the translation of the in vitro findings into an in vivo setting. Thus, the EV research field is moving from a technical focus to a more physiological focus, allowing for a deeper understanding of human physiology, development of diagnostic tools and potential treatment strategies for precision medicine. K E Y W O R D S exosomes, intercellular communication, microvesicles

Decreased Excretion of Urinary Exosomal Aquaporin-2 in a Puromycin Aminonucleoside-Induced Nephrotic Syndrome Model

“…Exosomes have been shown to carry membrane and cytosolic proteins, mRNAs, micro RNAs, long noncoding RNAs, and other molecules, and these molecule-laden exosomes are considered to play a role in intercellular communication under both physiological and pathological conditions [3][4][5][6]. Accumulative evidence has indicated that the relative abundance of these molecule-bearing urinary exosomes is altered in various kidney diseases [7]. In fact, it has been proposed that several exosome-derived molecules, such as aquaporins (AQPs) [8], miR-125a and miR-351 [6], RNA (MEG3) [9], RNA HOTAIR [4], and fetuin-A, could have potential application as biomarkers [10].…”

Mesenchymal Stem Cell Derived Extracellular Vesicles in Aging

“…They are involved in tissue homeostasis maintenance and repair. They may also reflect the pathological state of the releasing cells, making them promising biomarkers of diverse pathologies (Svenningsen et al, 2019). EVs are therefore attractive as biomarkers for diagnosis or prognosis purposes and as therapeutic agents with documented activities related to the parental cell origin.…”

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

“…Plasma EVs are one of the most promising biomarkers for solid organ transplantation, reducing or even obviating the need for renal biopsy (216)(217)(218).…”