Extracellular vesicles mediate cellular interactions in renal diseases—Novel views of intercellular communications in the kidney

Abstract

The kidney is a complicated and important internal organ receiving approximately 20% of the cardiac output and mediates numerous pathophysiologic actions. These include selectively filtering macromolecules of the blood, exquisite reclaimation of electrolyctes, urine concentration via an elegant osmotic mechanism, and excretion of an acid load. In addition, the renal tubules carry out secretory functions and produce hormones and cytokines. The kidney receives innervation and hormonal regulation. Therefore, dysfunction of the kidney leads to retention of metabolic waste products, and/or significant proteinuria and hematuria. In the past several decades, the role of extracellular vesicles (EVs) in intercellular communications, and the uptake of EVs by recipient cells through phagocytosis and endocytosis have been elucidated. The new knowledge on EVs expands over the classical mechanisms of cellular interaction, and may change our way of thinking of renal pathophysiology in the subcellular scale. Based on some ultrastructural discoveries in the kidney, this review will focus on the role of EVs in intercellular communications, their internalization by recipient cells, and their relationship to renal pathology.

Extracellular vesicles contribute to early cyst development in autosomal dominant polycystic kidney disease by cell‐to‐cell communication

“…[17][18][19] The role of EVs in kidney diseases has gained increasing attention. [20][21][22][23] EVs are a heterogenous group of nanoparticles released constitutively by all cell types. 24 Delimited by a double phospholipidic layer, EVs are classified in exosomes, microvesicles and apoptotic bodies.…”

“…The role of EVs in kidney diseases has gained increasing attention 20–23 . EVs are a heterogenous group of nanoparticles released constitutively by all cell types 24 .…”

“…25 Within the kidney, EVs are capable of acting as intercellular mediators between the proximal and distal segments of the nephron, and to exert their signaling effect in a paracrine and autocrine fashion. 21,23,26,27 Through these mechanisms, EVs have been shown to influence electrolyte transport 27 and their relevance is further highlighted by being involved in the development and progression of several kidney diseases, including ADPKD. 20,23 Recently, EVs have been proposed as an important player involved in intersegment signaling between cystic and precystic tubular cells.…”

Extracellular Vesicles as Source of Biomarkers in Glomerulonephritis

“…EVs carry a cargo of proteins, lipids, nucleic acids, and metabolites that acts as a mediator of cell-to-cell signaling in several physiological and pathological conditions [ 12 ], comprising inter-kingdom communication [ 13 ]. In recent years, the involvement of EVs in kidney disease has been a major topic of investigation [ 14 , 15 , 16 ]. Urinary EVs deeply impact the recipient cells participating in kidney development, playing a role in the physiology and pathology of the urinary tract [ 17 ].…”

Macrophages-Derived, LRG1-Enriched Extracellular Vesicles Exacerbate Aristolochic Acid Nephropathy Via A TGFβR1-Dependent Manner

“…Recent studies have revealed that EV may participate in renal tissue damage and regeneration through mediating inter-nephron communication (Karpman et al 2017, Tang et al 2019). Thus, the potential use of EV as therapeutic vector has gained considerable interest (Zhang and Liu 2021).…”