Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Dimuccio, Veronica; Bellucci, Linda; Genta, Marianna; Grange, Cristina; Brizzi, Maria Felice; Gili, Maddalena; Gallo, Sara; Centomo, Maria Laura; Collino, Federica; Bussolati, Benedetta

doi:10.3390/ijms232012098

Cited by 7 publications

(6 citation statements)

References 39 publications

(83 reference statements)

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“…27 MiR-126 is increased in urinederived extracellular vesicles released from renal epithelial cells undergoing mesenchymal transition and is associated with increased albuminuria, fibrosis, and progression in patients with DN. 28 In contrast, our data and studies on humans with DN documented a significant decrease in circulating miR-126 expression in dogs and patients with CKD when compared with controls (Table S5). 29,30 MiR-126 was enriched in endothelial progenitor cell-derived extracellular vesicles and is thought to be responsible, in part, for their protective effect against ischemic AKI.…”

Section: Discussioncontrasting

confidence: 60%

“…While no published literature currently exists regarding the expression of miR‐126 in ICGN, there is increased expression of urinary miR‐126 in patients with type 2 diabetes mellitus and DN compared with patients without DN 27 . MiR‐126 is increased in urine‐derived extracellular vesicles released from renal epithelial cells undergoing mesenchymal transition and is associated with increased albuminuria, fibrosis, and progression in patients with DN 28 . In contrast, our data and studies on humans with DN documented a significant decrease in circulating miR‐126 expression in dogs and patients with CKD when compared with controls (Table S5).…”

Section: Discussionmentioning

confidence: 99%

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MicroRNA‐126 in dogs with immune complex‐mediated glomerulonephritis

Cherry,

Chu,

Cianciolo

et al. 2023

Veterinary Internal Medicne

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BackgroundMost proteinuric dogs with naturally occurring chronic kidney disease have amyloidosis (AMYL), glomerulosclerosis (GS), or immune complex‐mediated glomerulonephritis (ICGN), each with different treatment and prognosis. A noninvasive and disease‐specific biomarker is lacking.HypothesisWe hypothesized that the expression pattern of biofluid microRNA (miRNAs and miRs) would correlate with disease progression and categorization.AnimalsArchived serum and urine samples from 18 dogs with glomerular disease and 6 clinically healthy dogs; archived urine samples from 49 dogs with glomerular disease and 13 clinically healthy dogs.MethodsRetrospective study. Archived biofluid samples from adult dogs with biopsy‐confirmed glomerular disease submitted to the International Veterinary Renal Pathology Service between 2008 and 2016 were selected. Serum and urinary miRNAs were isolated and profiled using RNA sequencing. Urinary miR‐126, miR‐21, miR‐182, and miR‐486 were quantified using quantitative reverse transcription PCR.ResultsWhen comparing more advanced disease with earlier disease, no serum miRNAs were differentially expressed, but urinary miR‐21 and miR‐182 were 1.63 (95% CI: .86‐3.1) and 1.45 (95% CI: .82‐2.6) times higher in azotemic dogs, respectively (adjusted P < .05) and weakly correlated with tubulointerstitial fibrosis (miR‐21: r = .32, P = .03; miR‐182: r = .28, P = .05). Expression of urinary miR‐126 was 10.5 (95% CI: 4.1‐26.7), 28.9 (95% CI: 10.5‐79.8), and 126.2 (95% CI: 44.7‐356.3) times higher in dogs with ICGN compared with dogs with GS, AMYL, and healthy controls, respectively (P < .001).Conclusions and Clinical ImportanceThe miR‐126 could help identify dogs that might benefit from immunosuppressive therapy in the absence of a biopsy. MiR‐21 and miR‐182 are potential markers of disease severity and fibrosis.

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Section: Discussioncontrasting

confidence: 60%

Section: Discussionmentioning

confidence: 99%

MicroRNA‐126 in dogs with immune complex‐mediated glomerulonephritis

Cherry,

Chu,

Cianciolo

et al. 2023

Veterinary Internal Medicne

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“…Podocytes and proximal tubular cell line HK-2 under renal damage condition develop EMT. In addition, these cells specifically exhibit elevated levels of miR-145 and miR-126 in EVs, in accordance with uEVs from diabetic nephropathy patients and lead to EMT progression [ 42 ].…”

Section: Urinary Extracellular Vesicles (Uevs) In Kidney Cancermentioning

confidence: 94%

Kidney Cancer and Potential Use of Urinary Extracellular Vesicles

Le,

Munir,

Kim

et al. 2024

Oncol.Rev.

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Kidney cancer is the 14th most common cancer globally. The 5-year relative survival rate of kidney cancer at a localized stage is 92.9% and it declines to 17.4% in metastatic stage. Currently, the most accurate method of its diagnosis is tissue biopsy. However, the invasive and costly nature of biopsies makes it undesirable in many patients. Therefore, novel biomarkers for diagnosis and prognosis should be explored. Urinary extracellular vesicles (uEVs) are small vesicles (50–200 nm) in urine carrying nucleic acids, proteins and lipids as their cargos. These uEVs’ cargos can provide non-invasive alternative to monitor kidney health. In this review, we have summarized recent studies investigating potential use of uEVs’ cargos as biomarkers in kidney cancer for diagnosis, prognosis and therapeutic intervention.

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“…Under TGF-β1 stimulation, podocytes, cultured in a millifluidic system with GECs, released EVs enriched of the profibrotic miR-145. On the contrary, EVs shed by GECs were associated with a relevant reduction in the proangiogenic miR-126 ( Table 1 ) ( 80 ).…”

Section: Role Of Evs In Kidney Diseasesmentioning

confidence: 99%

Exploring the role of urinary extracellular vesicles in kidney physiology, aging, and disease progression

Grange,

Dalmasso,

Cortez

et al. 2023

American Journal of Physiology-Cell Physiology

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Extracellular vesicles (EVs), membranous vesicles present in all body fluids, are considered important messengers, carrying their information over long distance and modulating the gene expression profile of recipient cells. EVs collected in urine (uEVs) are mainly originated from the apical part of urogenital tract, following the urine flow. Moreover, bacterial derived EVs are present within urine and may reflect the composition of microbiota. Consolidated evidence has established the involvement of uEVs in renal physiology, being responsible for glomerular and tubular cross-talk and among different tubular segments. uEVs may also be involved in other physiologic functions such as modulation of innate immunity, coagulation or metabolic activities. Furthermore, it has been recently remonstrated that age, sex, endurance excise and lifestyle may influence uEV composition and release, modifying their cargo. On the other hand, uEVs appear modulators of different urogenital pathological conditions, triggering disease progression. uEVs sustain fibrosis and inflammation processes, both involved in acute and chronic kidney diseases, ageing and stone formation. The molecular signature of uEVs collected from diseased patients can be of interest for understanding kidney physiopathology and for identifying diagnostic and prognostic biomarkers.

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Upregulation of miR145 and miR126 in EVs from Renal Cells Undergoing EMT and Urine of Diabetic Nephropathy Patients

Cited by 7 publications

References 39 publications

MicroRNA‐126 in dogs with immune complex‐mediated glomerulonephritis

MicroRNA‐126 in dogs with immune complex‐mediated glomerulonephritis

Kidney Cancer and Potential Use of Urinary Extracellular Vesicles

Exploring the role of urinary extracellular vesicles in kidney physiology, aging, and disease progression

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