Vesicles bearing gifts: the functional importance of micro-RNA transfer in extracellular vesicles in chronic kidney disease

Abbasian, Nima; Herbert, Karl E.; Pawluczyk, Izabella Z. A.; Burton, James O.; Bevington, Alan

doi:10.1152/ajprenal.00318.2018

Cited by 18 publications

(15 citation statements)

References 163 publications

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“…In addition, platelet microparticles (PMPs) are increased in CKD and dialysis patients [91] and have been reported to express 50-to 100-fold more procoagulant capacity than activated intact platelets, with the ability to activate the classical complement pathway. The microRNAs carried by vesicles from platelets, endothelial cells, and monocytes have potential inflammatory effects [172]. Further, the gut dysbiosis in CKD may play a role in the thromboembolic complication in CKD.…”

Section: Uremia Platelet Dysfunction and Alterations In Immunitymentioning

confidence: 99%

Endothelial Damage, Inflammation and Immunity in Chronic Kidney Disease

Díaz‐Ricart

Torramadé-Moix

Pascual

et al. 2020

Toxins

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Chronic kidney disease (CKD) patients have an accelerated atherosclerosis, increased risk of thrombotic-ischemic complications, and excessive mortality rates when compared with the general population. There is also evidence of an endothelial damage in which the proinflammatory state, the enhanced oxidative stress, or the accumulation of toxins due to their reduced renal clearance in uremia play a role. Further, there is evidence that uremic endothelial cells are both involved in and victims of the activation of the innate immunity. Uremic endothelial cells produce danger associated molecular patterns (DAMPS), which by binding to specific pattern recognition receptors expressed in multiple cells, including endothelial cells, induce the expression of adhesion molecules, the production of proinflammatory cytokines and an enhanced production of reactive oxygen species in endothelial cells, which constitute a link between immunity and inflammation. The connection between endothelial damage, inflammation and defective immunity in uremia will be reviewed here.

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Section: Uremia Platelet Dysfunction and Alterations In Immunitymentioning

confidence: 99%

Endothelial Damage, Inflammation and Immunity in Chronic Kidney Disease

Díaz‐Ricart

Torramadé-Moix

Pascual

et al. 2020

Toxins

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“…Several studies have linked circulating EVs released from renal endothelial cells to the progression of different kidney diseases such as acute kidney injury, CKD, diabetic nephropathy (DN), lupus nephritis, and nephrotic syndrome [9][10][11]. As urine is also a rich source of EVs [12], increased levels of urinary EVs provide a possible noninvasive indicator of kidney injuries [12,13]. Indeed, Burger et al [14] reported that podocytes release EVs in vitro when treated with high glucose for 24 h. Interestingly, the same group detected significant increases in podocyte-EVs in type 1 diabetes patients in the absence of albuminuria, nephrinuria, or glomerular filtration rate (GFR) decline [15], implying that urinary podocyte-EVs may be a more sensitive marker for podocyte injury than proteinuria.…”

Section: Introductionmentioning

confidence: 99%

Podocyte-Released Migrasomes in Urine Serve as an Indicator for Early Podocyte Injury

Liu

Rong

et al. 2020

Kidney Dis

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Background: Levels of urinary microvesicles, which are increased during various kidney injuries, have diagnostic potential for renal diseases. However, the significance of urinary microvesicles as a renal disease indicator is dampened by the difficulty to ascertain their cell source. Objectives: The aim of this study was to demonstrate that podocytes can release migrasomes, a unique class of microvesicle with size ranging between 400 and 2,000 nm, and the urine level of migrasomes may serve as novel non-invasive biomarker for early podocyte injury. Method: In this study, immunofluorescence labeling, electronic microscopy, nanosite, and sequential centrifugation were used to purify and analyze migrasomes. Results: Migrasomes released by podocytes differ from exosomes as they have different content and mechanism of release. Compared to podocytes, renal tubular cells secrete markedly less migrasomes. Moreover, secretion of migrasomes by human or murine podocytes was strongly augmented during podocyte injuries induced by LPS, puromycin amino nucleoside (PAN), or a high concentration of glucose (HG). LPS, PAN, or HG-induced podocyte migrasome release, however, was blocked by Rac-1 inhibitor. Strikingly, a higher level of podocyte migrasomes in urine was detected in mice with PAN-nephropathy than in control mice. In fact, increased urinary migrasome number was detected earlier than elevated proteinuria during PAN-nephropathy, suggesting that urinary migrasomes are a more sensitive podocyte injury indicator than proteinuria. Increased urinary migrasome number was also detected in diabetic nephropathy patients with proteinuria level <5.5 g/day. Conclusions: Our findings reveal that podocytes release the “injury-related” migrasomes during migration and provide urinary podocyte migrasome as a potential diagnostic marker for early podocyte injury.

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“…Although EVs appear to be associated with many diseases, their involvement in renal diseases (e.g., CKD) is especially strong (Tables 1 and 2). Several studies have also highlighted a major role for miRNA transported by EVs in CKD, as summarized by Abbasian et al [56]. Recently, Zietzer et al have identified an alteration of intercellular communication mediated by miRNA through EVs in CKD patients, thus promoting endothelial dysfunction [57].…”

Section: Evs and Ckdmentioning

confidence: 98%

“…Clinical and preclinical studies have highlighted the value of miRs (transported by EVs) as CKD biomarkers [56,106,[150][151][152][153][154][155][156][157][158][159]. Indeed, exosomes of patients with kidney diseases contain high levels of miR [152].…”

Section: Extracellular Vesicles As Biomarkers Of Ckdmentioning

confidence: 99%

Effects of Chronic Kidney Disease and Uremic Toxins on Extracellular Vesicle Biology

Yaker

Kamel

Ausseil

et al. 2020

Toxins

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Vascular calcification (VC) is a cardiovascular complication associated with a high mortality rate, especially in patients with diabetes, atherosclerosis or chronic kidney disease (CKD). In CKD patients, VC is associated with the accumulation of uremic toxins, such as indoxyl sulphate or inorganic phosphate, which can have a major impact in vascular remodeling. During VC, vascular smooth muscle cells (VSMCs) undergo an osteogenic switch and secrete extracellular vesicles (EVs) that are heterogeneous in terms of their origin and composition. Under physiological conditions, EVs are involved in cell-cell communication and the maintenance of cellular homeostasis. They contain high levels of calcification inhibitors, such as fetuin-A and matrix Gla protein. Under pathological conditions (and particularly in the presence of uremic toxins), the secreted EVs acquire a pro-calcifying profile and thereby act as nucleating foci for the crystallization of hydroxyapatite and the propagation of calcification. Here, we review the most recent findings on the EVs’ pathophysiological role in VC, the impact of uremic toxins on EV biogenesis and functions, the use of EVs as diagnostic biomarkers and the EVs’ therapeutic potential in CKD.

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Vesicles bearing gifts: the functional importance of micro-RNA transfer in extracellular vesicles in chronic kidney disease

Cited by 18 publications

References 163 publications

Endothelial Damage, Inflammation and Immunity in Chronic Kidney Disease

Endothelial Damage, Inflammation and Immunity in Chronic Kidney Disease

Podocyte-Released Migrasomes in Urine Serve as an Indicator for Early Podocyte Injury

Effects of Chronic Kidney Disease and Uremic Toxins on Extracellular Vesicle Biology

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