Abstract

Intercellular communication governs multicellular interactions in complex organisms. A variety of mechanisms exist through which cells can communicate, e.g., cell-cell contact, the release of paracrine/autocrine soluble molecules, or the transfer of extracellular vesicles (EVs). EVs are membrane-surrounded structures released by almost all cell types, acting both nearby and distant from their tissue/organ of origin. In the kidney, EVs are potent intercellular messengers released by all urinary system cells and are involved in cell crosstalk, contributing to physiology and pathogenesis. Moreover, urine is a reservoir of EVs coming from the circulation after crossing the glomerular filtration barrier—or originating in the kidney. Thus, urine represents an alternative source for biomarkers in kidney-related diseases, potentially replacing standard diagnostic techniques, including kidney biopsy. This review will present an overview of EV biogenesis and classification and the leading procedures for isolating EVs from body fluids. Furthermore, their role in intra-nephron communication and their use as a diagnostic tool for precision medicine in kidney-related disorders will be discussed.

Highlights

  • It was demonstrated that glomerular endothelial cells (GEC), after exposure to high glucose concentration, released extracellular vesicles (EVs) enriched with transforming growth factor (TGF) β1 mRNA

  • The results suggested that miR-194-5p and miR-23b-3p were correlated with urine protein content and could reflect the severity of the disease [99]

  • EVs are active biological agents that play an essential role in intercellular communication, showing beneficial or detrimental effects on recipient cells based on their origin

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Urinary peptides [3] and microRNAs (miRNAs) [4] have been suggested as valid alternative markers to classical biochemical measurements [5] of kidney disease progression Both proteins and miRNAs have been described to be relatively stable in biological fluids, mainly when carried by extracellular vesicles (EVs). Some of the fundamental qualities of a promising biomarker include good stability, easy accessibility, and the absence of invasiveness during its collection [10] Based on this approach, EVs could represent an innovative tool for the so-called liquid biopsy, a technique allowing clinicians to screen nonsolid biological tissues such as blood or urine, searching for markers to assess a patient’s condition [11]. This review will present an overview of EV classification and isolation procedures, their role in intra-nephron communication, and their use as a diagnostic tool for precision medicine in kidney-related disorders

Extracellular Vesicles
Isolation Method
The Molecular Content of EVs
Methods of EV Isolation
EVs in the Kidney
EVs and Glomerulus
EVs and Kidney Tubules
EVs in Communication from Different Nephron Sections
Non-Kidney Cell EVs in Intra-Renal Communication
Main Results
13 LN patients and miR-26a
30 HD and 30 T1D miR-424 and miR-218 combined centrifugation
UPJO and 3 healthy fetusis
Nephrotic Syndrome
Nephritic Syndrome
Ciliopathies
Tubulopathies
Diabetic Nephropathy
Obstructive Nephropathy
EVs in Clinics
Conclusions
Findings
Methods
Full Text
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