Novel Aspects of Extracellular Vesicles in the Regulation of Renal Physiological and Pathophysiological Processes

Abstract

Extracellular vesicles (EV) are nanosized particles released by a large variety of cells. They carry molecules such as proteins, RNA and lipids. While urinary EVs have been longer studied as a source of biomarkers for renal and non-renal disorders, research on EVs as regulatory players of renal physiological and pathological processes has experienced an outbreak recently in the past decade. In general, the microenvironment and (patho)physiological state of the donor cells affect the cargo of the EVs released, which then determines the effect of these EVs once they reach a target cell. For instance, EVs released by renal epithelial cells modulate the expression and function of water and solute transporting proteins in other cells. Also, EVs have been demonstrated to regulate renal organogenesis and blood flow. Furthermore, a dual role of EVs promoting, but also counteracting, disease has also been reported. EVs released by renal tubular cells can reach fibroblasts, monocytes, macrophages, T cells and natural killer cells, thus influencing the pathogenesis and progression of renal disorders like acute kidney injury and fibrosis, nephrolithiasis, renal transplant rejection and renal cancer, among others. On the contrary, EVs may also exert a cytoprotective role upon renal damage and promote recovery of renal function. In the current review, a systematic summary of the key studies from the past 5 years addressing the role of EVs in the modulation of renal physiological and pathophysiological processes is provided, highlighting open questions and discussing the potential of future research.

New Insights Into the Role and Mechanism of Partial Epithelial-Mesenchymal Transition in Kidney Fibrosis

“…Extracellular vesicles (EVs) such as exosomes are important mediators of cell-cell communication that act by transmitting proteins and genetic information. Vesicles incorporate molecules from their origin cells containing proteins, nucleic acids and lipids (Rigalli et al, 2020). A recent study demonstrated that exosomes are produced in renal proximal tubular epithelium following various fibrotic injury (UUO, ischemia/reperfusion or Liu, 2010;Lee and Nelson, 2012;LeBleu et al, 2013 Partial EMT Concept of partial EMT TECs expressed both markers of epithelial and mesenchymal cells while remained attached to the basement membrane during fibrosis.…”

Normothermic kidney perfusion: An overview of protocols and strategies

“…The pattern of perfusion parameters (flow and resistance) and the measurement of biomarkers such as neutrophil gelatinase lipocalin, liver fatty acid binding protein and inflammatory cytokines (IL‐6, IL‐8, IL‐18) could be helpful in determining the level of injury and in predicting outcome in these cases and for more prolonged periods of NMP. Recently reported new biomarkers, such as extracellular vesicles, microRNAs, and nanoparticles derived from blood/urine or imaging technologies to assess the microcirculation could be applied to assess viability during NMP in the future 45,46 …”

Major signaling pathways and key mediators of macrophages in acute kidney injury (Review)

“…Extracellular vesicles (EVs) refer to the membrane structures released by all types of cells through different biogenic pathways ( 120 ). EVs are intercellular messengers that are involved in a wide range of physiological and pathological processes ( 121 ). EVs have the advantages of exhibiting stable physical and chemical properties ( 122 ).…”

“…In addition, blocking the exosome-mediated transfer of miR-23a between RTECs and macrophages may be an innovative method for enhancing renal tubulointerstitial inflammation. In summary, exosomes are involved in adjusting the routine function of the kidney, as well as in promoting and inhibiting various pathophysiological reactions ( 121 ).…”