Circulating argonaute-bound microRNA-126 reports vascular dysfunction and treatment response in acute and chronic kidney disease

Scullion, Kathleen; Vliegenthart, A. D. Bastiaan; Rivoli, Laura; Oosthuyzen, Wilna; Farrah, Tariq E.; Czopek, Alicja; Webb, David J.; Hunter, Robert W.; Bailey, Matthew A.; Dhaun, Neeraj; Dear, James W.

doi:10.1016/j.isci.2020.101937

Cited by 18 publications

(12 citation statements)

References 51 publications

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“…Moreover, miRNAs participate in cellular process, including the growth of renal tubular epithelial cells ( 13 , 14 ). Meanwhile, miRNAs have been reported to be associated with AKI progression ( 15 – 17 ). For instance, miR-21 has been shown to inhibit the progression of AKI ( 18 ); Jiang et al ( 19 ) found that miR-500a-3p alleviated kidney injury by targeting mixed lineage kinase domain like pseudokinase.…”

Section: Introductionmentioning

confidence: 99%

Exosomal‑miR‑1184 derived from mesenchymal stem cells alleviates cisplatin‑associated acute kidney injury

Zhang

Zheng

et al. 2021

Mol Med Rep

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Acute kidney injury (AKI) poses a severe threat to human health. MicroRNAs (miRNAs/miRs) are known to be involved in the progression of AKI; however, the function of miR-1184 in AKI remains unclear. Thus, the aim of the present study was to examine the role of this miRNA in kidney injury. In order to mimic AKI in vitro , HK-2 cells were treated with cisplatin. Bioinformatics analysis was performed to explore the differentially expressed miRNAs in AKI. A Cell Counting Kit-8 assay and flow cytometry were performed to examine cell viability and apoptosis, respectively. mRNA expression levels were detected via reverse transcription-quantitative PCR, and protein levels were investigated by western blot analysis. ELISA was performed to examine the levels of IL-1β and TNF-α in the cell supernatants. The results revealed that miR-1184 expression was downregulated in AKI. Exosomes derived from miR-1184 agomir-treated mesenchymal stem cells (MSCs) significantly reversed cisplatin-induced cell growth inhibition by inhibiting apoptosis. Moreover, forkhead box O4 (FOXO4) was found to be the direct target of miR-1184, and exosomes expressing miR-1184 notably inhibited cisplatin-induced inflammatory responses in HK-2 cells via the mediation of IL-1β and TNF-α. Furthermore, exosomes derived from miR-1184 agomir-treated MSCs significantly induced G 1 phase arrest in HK-2 cells via the regulation of FOXO4, p27 Kip1 and CDK2. In conclusion, the present study demonstrated that exosomal-miR-1184 derived from MSCs alleviates cisplatin-associated AKI. Thus, the findings presented herein may shed new light onto the exploration of novel strategies for the treatment of AKI.

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Section: Introductionmentioning

confidence: 99%

Exosomal‑miR‑1184 derived from mesenchymal stem cells alleviates cisplatin‑associated acute kidney injury

Zhang

Zheng

et al. 2021

Mol Med Rep

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“…This information did not, however, exclude a potential role of miR-126 in the pathophysiology of CKD, thus we wanted to further explore this hypothesis in the present follow-up study. In support of this, Scullion et al recently showed that miR-126 serum was reduced in rats with nephrotoxic nephritis and in humans with both acute endothelial and renal injury compared to healthy controls [ 11 ]. Furthermore, in this work, miR-126 increased dramatically post-treatment but remained lower than in healthy animals.…”

Section: Discussionmentioning

confidence: 94%

“…Additionally, we have described a clear link between miR-126 and vascular injury in CKD models [ 7 , 8 , 23 ], as well as a decrease in the serum levels of this miRNA in CKD patients [ 6 ]. In addition, Scullion et al found a strong correlation between (1) circulating miR-126 and (2) pulse-wave velocity and Asymmetric Dimethylarginine (ADMA), both markers of endothelial function [ 11 ]. Our novel results strengthen the hypothesis of a link between miR-126 levels and endothelial dysfunction in a large cohort of CKD patients.…”

Section: Discussionmentioning

confidence: 99%

“…Serum levels of both miRNAs was associated with all-cause mortality, but also with CV and renal events. A failure in the regulatory role of mR-126 in endothelial function during CKD has thus been suggested [ 7 , 8 , 9 , 10 , 11 ]. To better understand the role of this non-coding RNA in progressing stages of CKD, we aimed in this work to correlate its expression with markers of endothelial dysfunction, on one hand, and uremic toxins, on the other hand.…”

Section: Introductionmentioning

confidence: 99%

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Syndecan-1 and Free Indoxyl Sulfate Levels Are Associated with miR-126 in Chronic Kidney Disease

Fourdinier

Glorieux

Brigant

et al. 2021

IJMS

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Chronic kidney disease (CKD) is a major cause of death worldwide and is associated with a high risk for cardiovascular and all-cause mortality. In CKD, endothelial dysfunction occurs and uremic toxins accumulate in the blood. miR-126 is a regulator of endothelial dysfunction and its blood level is decreased in CKD patients. In order to obtain a better understanding of the physiopathology of the disease, we correlated the levels of miR-126 with several markers of endothelial dysfunction, as well as the representative uremic toxins, in a large cohort of CKD patients at all stages of the disease. Using a univariate analysis, we found a correlation between eGFR and most markers of endothelial dysfunction markers evaluated in this study. An association of miR-126 with all the evaluated uremic toxins was also found, while uremic toxins were not associated with the internal control, specifically cel-miR-39. The correlation between the expression of endothelial dysfunction biomarker Syndecan-1, free indoxyl sulfate, and total p-cresyl glucuronide on one side, and miR-126 on the other side was confirmed using multivariate analysis. As CKD is associated with reduced endothelial glycocalyx (eGC), our results justify further evaluation of the role of correlated parameters in the pathophysiology of CKD.

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“…A similar trend was observed in a study looking at circulating miR-126 decrease as a biomarker for vascular dysfunction. Whilst large variation was seen in healthy and patient cohorts, miR-126 remained 88-fold lower in vasculitis patients than controls, suggesting its use as a potential vascular injury marker (Scullion et al 2021).…”

Section: Inter-and Intra-individual Variability In Basal Mir Expressionmentioning

confidence: 99%

Systems analysis of miRNA biomarkers to inform drug safety

Schofield

Brown

et al. 2021

Arch Toxicol

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AbstractmicroRNAs (miRNAs or miRs) are short non-coding RNA molecules which have been shown to be dysregulated and released into the extracellular milieu as a result of many drug and non-drug-induced pathologies in different organ systems. Consequently, circulating miRs have been proposed as useful biomarkers of many disease states, including drug-induced tissue injury. miRs have shown potential to support or even replace the existing traditional biomarkers of drug-induced toxicity in terms of sensitivity and specificity, and there is some evidence for their improved diagnostic and prognostic value. However, several pre-analytical and analytical challenges, mainly associated with assay standardization, require solutions before circulating miRs can be successfully translated into the clinic. This review will consider the value and potential for the use of circulating miRs in drug-safety assessment and describe a systems approach to the analysis of the miRNAome in the discovery setting, as well as highlighting standardization issues that at this stage prevent their clinical use as biomarkers. Highlighting these challenges will hopefully drive future research into finding appropriate solutions, and eventually circulating miRs may be translated to the clinic where their undoubted biomarker potential can be used to benefit patients in rapid, easy to use, point-of-care test systems.

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Circulating argonaute-bound microRNA-126 reports vascular dysfunction and treatment response in acute and chronic kidney disease

Cited by 18 publications

References 51 publications

Exosomal‑miR‑1184 derived from mesenchymal stem cells alleviates cisplatin‑associated acute kidney injury

Exosomal‑miR‑1184 derived from mesenchymal stem cells alleviates cisplatin‑associated acute kidney injury

Syndecan-1 and Free Indoxyl Sulfate Levels Are Associated with miR-126 in Chronic Kidney Disease

Systems analysis of miRNA biomarkers to inform drug safety

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