New insight into the role of extracellular vesicles in kidney disease

Lv, Lin‐Li; Feng, Yan; Tang, Tao-Tao; Liu, Bi-Cheng

doi:10.1111/jcmm.14101

Cited by 64 publications

(78 citation statements)

References 83 publications

(149 reference statements)

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“…EVs are involved in the origin and development of various pathologies, and may be used as potential biomarkers or therapeutic agents in patients with CVDs (Amosse et al, 2017;Jansen et al, 2017;Dickhout and Koenen, 2018). EVs are involved in the development of renal dysfunction (Karpman et al, 2017;Lv et al, 2019), and can, therefore, be used in the diagnosis of, and therapy against, these diseases (Zhang et al, 2016). Elimination of EVs is currently used as a therapeutic strategy .…”

Section: Cellular Alterations In the Vascular System Of Patients Withmentioning

confidence: 99%

“…Not only are plasma EVs modified in kidney diseases, but the release of EVs from renal cells (epithelial cells, podocytes, and tubular cells) is also altered. These kidneyderived EVs can be isolated from urine and used as biomarkers of CKD (Lv et al, 2019). Proteomic analyses have shown differences in urinary EVs obtained from patients with kidney diseases (Bruschi et al, 2019).…”

Section: Cellular Alterations In the Vascular System Of Patients Withmentioning

confidence: 99%

“…In addition to serving as biomarkers, blood and urinary MVs play functional and therapeutic roles in renal diseases (Erdbrügger and Le, 2016;Kwon, 2019). For example, blood EVs influence renal physiology via intranephron communication (Lv et al, 2019), and their antibacterial (Hiemstra et al, 2014) and protective effects (Bruno et al, 2009(Bruno et al, , 2016Rovira et al, 2017) have been demonstrated in kidney diseases. ROS are important in the origination and development of CKD, while MVs play antioxidative roles in this condition .…”

Section: Cellular Alterations In the Vascular System Of Patients Withmentioning

confidence: 99%

See 2 more Smart Citations

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Carracedo

Alique

Vida

et al. 2020

Front. Cell Dev. Biol.

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Cardiovascular diseases (CVDs), especially those involving a systemic inflammatory process such as atherosclerosis, remain the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). CKD is a systemic condition affecting approximately 10% of the general population. The prevalence of CKD has increased over the past decades because of the aging of the population worldwide. Indeed, CVDs in patients with CKD constitute a premature form of CVD observed in the general population. Multiple studies indicate that patients with renal disease undergo accelerated aging, which precipitates the appearance of pathologies, including CVDs, usually associated with advanced age. In this review, we discuss several aspects that characterize CKD-associated CVDs, such as etiopathogenic elements that CKD patients share with the general population, changes in the cellular balance of reactive oxygen species (ROS), and the associated process of cellular senescence. Uremiaassociated aging is linked with numerous changes at the cellular and molecular level. These changes are similar to those observed in the normal process of physiologic aging. We also discuss new perspectives in the study of CKD-associated CVDs and epigenetic alterations in intercellular signaling, mediated by microRNAs and/or extracellular vesicles (EVs), which promote vascular damage and subsequent development of CVD. Understanding the processes and factors involved in accelerated senescence and other abnormal intercellular signaling will identify new therapeutic targets and lead to improved methods of diagnosis and monitoring for patients with CKD-associated CVDs.

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Section: Cellular Alterations In the Vascular System Of Patients Withmentioning

confidence: 99%

Section: Cellular Alterations In the Vascular System Of Patients Withmentioning

confidence: 99%

Section: Cellular Alterations In the Vascular System Of Patients Withmentioning

confidence: 99%

See 1 more Smart Citation

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Carracedo

Alique

Vida

et al. 2020

Front. Cell Dev. Biol.

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“…In the urine, these vesicles mostly originate from the surrounding renal cells (Pisitkun et al, 2004) and are named as "urinary exosomes." Hence, urinary exosomal miRs may provide crucial information about renal health (Alvarez et al, 2013;Erdbrugger and Le, 2016;Lv et al, 2019). In addition, miRs encapsulated in uEs are protected from the toxic effect of the urinary environment.…”

Section: Introductionmentioning

confidence: 99%

miR-451 Loaded Exosomes Are Released by the Renal Cells in Response to Injury and Associated With Reduced Kidney Function in Human

et al. 2020

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Micro-RNAs (miRs) encapsulated inside urinary exosomes (uEs) have the potential as early biomarkers. Previously, we reported that a rise in uE miR-451 predicted albuminuria in diabetic rats; however, whether the rise was protective or detrimental, and occurred in response to injury or general hyperglycemia, was unknown. To address this, we studied both human and rat models of renal disease. In humans, uE miR-451 was approximately twofold higher in subjects with early-stage chronic kidney disease (CKD; serum creatinine < 2.0 mg/dl; n = 28), as compared to age-matched healthy controls (n = 23), and had a significant negative correlation with estimated glomerular filtration rate (eGFR) (r 2 = −0.10, p = 0.01). Subgroup analysis of CKD subjects showed that those without diabetes had slightly (∼30%) but significantly higher uE miR-451 as compared to those with diabetes, with no differences in albumin excretion, eGFR, serum sodium, and potassium. Using human proximal tubule (hPT) cells, we found that locked nucleic acid (LNA) inhibition of miR-451 resulted in a significant increase in the messenger RNA (mRNA) expression of kidney-injury-associated miR-451 targets, e.g., CAB39, TBX1, and YWHAZ, as compared to treatment with a control LNA. Moreover, hPT cells and their secreted exosomes showed an increase in miR-451 in response to mechanical injury but not high glucose (20 versus 5 mM). For further proof of concept, in diabetic rats, we showed that atorvastatin (AT), a treatment proven to attenuate renal injury without affecting systemic glucose levels, reduced uE miR-451 with the concomitant restoration of renal miR-451. These data elucidate the stimuli for renal miR-451 expression and exosomal release and support its role as a therapeutic target and early biomarker for renal injury in humans.

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“…Extracellular vesicles (EVs or microparticles) is a general term that refers to membrane structures released by all cell types through different biogenesis pathways; EVs are secreted after fusion of endosomes with the plasma membrane (exosomes), shed from plasma membrane (microvesicles), or released during apoptosis (apoptotic bodies). These three entities differ in size (exosomes, 30-150 nm; shedding microvesicles, 150 nm−1 µm; apoptotic bodies, 1-5 µm) and partly in content (1)(2)(3)(4). In this review, we will employ the umbrella term "EVs" to include all the above-mentioned types of secreted membrane vesicles.…”

Section: Introductionmentioning

confidence: 99%

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

et al. 2020

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Extracellular vesicles (EVs) are known immune-modulators exerting a critical role in kidney transplantation (KT). EV bioactive cargo includes graft antigens, costimulatory/inhibitory molecules, cytokines, growth factors, and functional microRNAs (miRNAs) that may modulate expression of recipient cell genes. As paracrine factors, neutrophil-and macrophage-derived EVs exert immunosuppressive and immune-stimulating effects on dendritic cells, respectively. Dendritic cell-derived EVs mediate alloantigen spreading and modulate antigen presentation to T lymphocytes. At systemic level, EVs exert pleiotropic effects on complement and coagulation. Depending on their biogenesis, they can amplify complement activation or shed complement inhibitors and prevent cell lysis. Likewise, endothelial-and platelet-derived EVs can exert procoagulant/prothrombotic effects and also promote endothelial survival and angiogenesis after ischemic injury. Kidney endothelial-and tubular-derived EVs play a key role in ischemia-reperfusion injury (IRI) and during the healing process; additionally, they can trigger rejection by inducing both alloimmune and autoimmune responses. Endothelial EVs have procoagulant/pro-inflammatory effects and can release sequestered self-antigens, generating a tissue-specific autoimmunity. Renal tubule-derived EVs shuttle pro-fibrotic mediators (TGF-β and miR-21) to interstitial fibroblasts and modulate neutrophil and T-lymphocyte influx. These processes can lead to peritubular capillary rarefaction and interstitial fibrosis-tubular atrophy. Different EVs, including those from mesenchymal stromal cells (MSCs), have been employed as a therapeutic tool in experimental models of rejection and IRI. These particles protect tubular and endothelial cells (by inhibition of apoptosis and inflammation-fibrogenesis or by inducing autophagy) and stimulate tissue regeneration (by triggering angiogenesis, cell proliferation, and migration). Finally, urinary and serum EVs represent potential biomarkers for delayed graft function (DGF) and acute rejection. In conclusion, EVs sustain an intricate crosstalk between graft tissue and innate/adaptive immune systems. EVs play a major role in allorecognition, IRI, autoimmunity, and alloimmunity and are promising as biomarkers and therapeutic tools in KT.

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New insight into the role of extracellular vesicles in kidney disease

Cited by 64 publications

References 83 publications

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

Mechanisms of Cardiovascular Disorders in Patients With Chronic Kidney Disease: A Process Related to Accelerated Senescence

miR-451 Loaded Exosomes Are Released by the Renal Cells in Response to Injury and Associated With Reduced Kidney Function in Human

Extracellular Vesicles as Mediators of Cellular Crosstalk Between Immune System and Kidney Graft

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