Exosomes and microvesicles in normal physiology, pathophysiology, and renal diseases

Abstract

Extracellular vesicles are cell-derived membrane particles ranging from 30 to 5,000 nm in size, including exosomes, microvesicles, and apoptotic bodies. They are released under physiological conditions, but also upon cellular activation, senescence, and apoptosis. They play an important role in intercellular communication. Their release may also maintain cellular integrity by ridding the cell of damaging substances. This review describes the biogenesis, uptake, and detection of extracellular vesicles in addition to the impact that they have on recipient cells, focusing on mechanisms important in the pathophysiology of kidney diseases, such as thrombosis, angiogenesis, tissue regeneration, immune modulation, and inflammation. In kidney diseases, extracellular vesicles may be utilized as biomarkers, as they are detected in both blood and urine. Furthermore, they may contribute to the pathophysiology of renal disease while also having beneficial effects associated with tissue repair. Because of their role in the promotion of thrombosis, inflammation, and immune-mediated disease, they could be the target of drug therapy, whereas their favorable effects could be utilized therapeutically in acute and chronic kidney injury.

Keywords: Exosomes; Extracellular vesicles; Inflammation; Kidney; Microvesicles; Thrombosis.

Fig. 1

Schematic presentation of the release and uptake of extracellular vesicles. a Exosomes are released from late endosomes termed multivesicular bodies bearing intraluminal vesicles (ILVs) intracellularly. When the multivesicular bodies fuse with the plasma membrane and empty their contents, ILVs are released and are termed exosomes once they are extracellular. Exosomes are the smallest extracellular vesicles (Table 1). b Microvesicles are shed directly from the plasma membrane, thereby carrying membrane markers of the parent cell. Microvesicle formation is calcium-dependent and associated with loss of membrane asymmetry and disruption of the cellular cytoskeleton. c Extracellular vesicle uptake by target cells may occur via fusion of the vesicle membrane with the cell membrane or by endocytosis. The vesicle may also transduce an intracellular signal by ligand binding to a receptor on the recipient cell