Cellular origin and microRNA profiles of circulating extracellular vesicles in different stages of diabetic nephropathy

Uil, Melissa; Hau, Chi M.; Ahdi, Mohamed; Kers, Jesper; Saleem, Moin A.; Florquin, Sandrine; Gerdes, Victor E. A.; Nieuwland, Rienk; Roelofs, Joris J T H

doi:10.1093/ckj/sfz145

Cited by 20 publications

(15 citation statements)

References 51 publications

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“…In vitro, EVs rich in miR-21 improved endothelial barrier formation of cells cultured in serum from patients with DM and DKD [ 97 ]. Similar studies by Uil M et al described the upregulation of miR-99a-5p in EVs of macroalbuminuric patients compared with normo- and microalbuminuric subjects [ 95 ]. Moreover, the transfection of the miR-99a-5p mimic to cultured podocytes induced a downregulation of mTOR and the injury marker vimentin, suggesting a protective effect of miR-99a-5p on glomerular cells [ 95 ].…”

Section: Circulating Evs In Diabetic Kidney Diseasesupporting

confidence: 56%

“…Similar studies by Uil M et al described the upregulation of miR-99a-5p in EVs of macroalbuminuric patients compared with normo- and microalbuminuric subjects [ 95 ]. Moreover, the transfection of the miR-99a-5p mimic to cultured podocytes induced a downregulation of mTOR and the injury marker vimentin, suggesting a protective effect of miR-99a-5p on glomerular cells [ 95 ]. Sequencing of circulating EVs found a different miRNA profile in healthy volunteers compared to diabetic patients with DKD [ 98 ].…”

Section: Circulating Evs In Diabetic Kidney Diseasesupporting

confidence: 56%

“…Circulating EVs, although to a lesser extent than uEVs, have been also investigated as biomarkers for DKD diagnosis. In this regard, increased levels of platelet-, erythrocyte-, leukocyte-, and endothelial-derived EVs have been reported in DKD patients compared to controls [ 93 , 94 , 95 ]. The role of platelet-derived EVs in GEC dysfunction was also investigated in an experimental model of streptozotocin-induced diabetes in rats by Zhang Y et al [ 96 ].…”

Section: Circulating Evs In Diabetic Kidney Diseasementioning

confidence: 99%

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Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

Saenz-Pipaon

Echeverria

Orbe

et al. 2021

JCM

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Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in developed countries, affecting more than 40% of diabetes mellitus (DM) patients. DKD pathogenesis is multifactorial leading to a clinical presentation characterized by proteinuria, hypertension, and a gradual reduction in kidney function, accompanied by a high incidence of cardiovascular (CV) events and mortality. Unlike other diabetes-related complications, DKD prevalence has failed to decline over the past 30 years, becoming a growing socioeconomic burden. Treatments controlling glucose levels, albuminuria and blood pressure may slow down DKD evolution and reduce CV events, but are not able to completely halt its progression. Moreover, one in five patients with diabetes develop DKD in the absence of albuminuria, and in others nephropathy goes unrecognized at the time of diagnosis, urging to find novel noninvasive and more precise early diagnosis and prognosis biomarkers and therapeutic targets for these patient subgroups. Extracellular vesicles (EVs), especially urinary (u)EVs, have emerged as an alternative for this purpose, as changes in their numbers and composition have been reported in clinical conditions involving DM and renal diseases. In this review, we will summarize the current knowledge on the role of (u)EVs in DKD.

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Section: Circulating Evs In Diabetic Kidney Diseasesupporting

confidence: 56%

Section: Circulating Evs In Diabetic Kidney Diseasesupporting

confidence: 56%

Section: Circulating Evs In Diabetic Kidney Diseasementioning

confidence: 99%

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Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

Saenz-Pipaon

Echeverria

Orbe

et al. 2021

JCM

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“…Studies have increasingly proven that the expression of circulating miRNAs is dysregulated in various diseases, and miRNAs have been considered promising novel biomarkers for the diagnosis and monitoring of almost all diseases, including DN. [22][23][24][25] The miR-29 family comprises miR-29a, miR-29b and miR-29c, of which miR-29a and miR-29b are transcribed from chromosome 7q32. In this study, we found that the basic indicators of blood pressure and serum lipids in the T2DM patients were significantly increased compared with those in the healthy subjects.…”

Section: Discussionmentioning

confidence: 99%

“…MicroRNAs (miRNAs) constitute a group of noncoding singlestranded small RNA molecules with a length of approximately [21][22][23][24][25] nucleotides that can regulate the expression of target genes through the complete or partial complementary binding of the 3' untranslated region of the target messenger RNA. 7,8 Strikingly, human serum/plasma contains numerous stably expressed miRNAs and has the biological properties of resistance to RNase activity; thus, miR-NAs derived from peripheral blood have the potential to become noninvasive biomarkers of various diseases.…”

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confidence: 99%

Significance of serum miR‐29a in the occurrence and progression of diabetic nephropathy: A cross‐sectional study

Liu

Wang²,

et al. 2021

Clinical Laboratory Analysis

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Type 2 diabetes mellitus (T2DM) is a common metabolic disease that threatens human health, and as it progresses, it often causes a series of microvascular complications. [1][2][3] Diabetic nephropathy (DN), one of the most common microvascular complications of T2DM, is an important factor causing chronic kidney disease and has been reported to occur in approximately 40% of T2DM patients. 4 Although the

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An in vitro approach to understand contribution of kidney cells to human urinary extracellular vesicles

Barreiro

Lay

Leparc

et al. 2023

J of Extracellular Vesicle

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Extracellular vesicles (EV) are membranous particles secreted by all cells and found in body fluids. Established EV contents include a variety of RNA species, proteins, lipids and metabolites that are considered to reflect the physiological status of their parental cells. However, to date, little is known about cell‐type enriched EV cargo in complex EV mixtures, especially in urine. To test whether EV secretion from distinct human kidney cells in culture differ and can recapitulate findings in normal urine, we comprehensively analysed EV components, (particularly miRNAs, long RNAs and protein) from conditionally immortalised human kidney cell lines (podocyte, glomerular endothelial, mesangial and proximal tubular cells) and compared to EV secreted in human urine. EV from cell culture media derived from immortalised kidney cells were isolated by hydrostatic filtration dialysis (HFD) and characterised by electron microscopy (EM), nanoparticle tracking analysis (NTA) and Western blotting (WB). RNA was isolated from EV and subjected to miRNA and RNA sequencing and proteins were profiled by tandem mass tag proteomics. Representative sets of EV miRNAs, RNAs and proteins were detected in each cell type and compared to human urinary EV isolates (uEV), EV cargo database, kidney biopsy bulk RNA sequencing and proteomics, and single‐cell transcriptomics. This revealed that a high proportion of the in vitro EV signatures were also found in in vivo datasets. Thus, highlighting the robustness of our in vitro model and showing that this approach enables the dissection of cell type specific EV cargo in biofluids and the potential identification of cell‐type specific EV biomarkers of kidney disease.

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Cellular origin and microRNA profiles of circulating extracellular vesicles in different stages of diabetic nephropathy

Cited by 20 publications

References 51 publications

Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

Urinary Extracellular Vesicles for Diabetic Kidney Disease Diagnosis

Significance of serum miR‐29a in the occurrence and progression of diabetic nephropathy: A cross‐sectional study

An in vitro approach to understand contribution of kidney cells to human urinary extracellular vesicles

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