MiRNA profiling of urinary exosomes to assess the progression of acute kidney injury
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ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE124669 | GEO | 2019/01/05
REPOSITORIES: GEO
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Project description:Because exosomes have gained attention as a source of biomarkers, we investigated if miRNAs in exosomes (exo-miRs) can report the disease progression of organ injury. Using renal ischemia-reperfusion injury (IRI) as a model of acute kidney injury (AKI), we determined temporally-released exo-miRs in urine during IRI and found that these exo-miRs could reliably mirror the progression of AKI. From the longitudinal measurements of miRNA expression in kidney and urine, we found that release of exo-miRs was regulated sorting process, rather than simply representing their intracellular biosynthesis. In the injury state, miR-16, miR-24, and miR-200c were increased in the urine. Interestingly, expression of target mRNAs of these exo-miRs was significantly altered in renal medulla. Next, in the early recovery state, urinary exo-miRs (miR-9a, miR-141, miR-200a, miR-200c, miR-429), which shares Zeb1/2 as a common target mRNA, were upregulated, indicating that they reflect TGF--associated renal fibrosis. Finally, release of exo-miRs (miR-125a, miR-351) was regulated by TGF-1 and was able to differentiate the sham and IRI even after the injured kidneys were functionally recovered. Altogether, these data indicate that exo-miRs released in renal IRI are largely associated with TGF- signaling. Temporal release of exo-miRs which share targets might be a regulatory mechanism to control the disease progression of AKI.
2019-03-01 | GSE125305 | GEO
Project description:Aims: Mesenchymal stem cells (MSCs) gradually become attractive candidates for cardiac inflammation modulation, yet understanding of the mechanism remains elusive. Strikingly, recent studies indicated that exosomes secreted by MSCs might be a novel mechanism for the beneficial effect of MSCs transplantation after myocardial infarction. We therefore explored the role of MSC-derived exosomes (MSC-Exo) in the immunomodulation of macrophages after myocardial ischemia-reperfusion and its implications in cardiac injury repair. Methods and Results: Exosomes were isolated from the supernatant of MSCs using a gradient centrifugation method. Administration of MSC-Exo through intramyocardial injection after myocardial ischemia reperfusion reduced infarct size and alleviated inflammation level in heart and serum. Systemic depletion of macrophages with clodronate liposomes abolished the curative effects of MSC-Exo. MSC-Exo modified the polarization of M1 macrophages to M2 macrophages both in vivo and in vitro. miRNA-sequencing of MSC-Exo and bioinformatics analysis implicated miR-182 as a potent candidate mediator of macrophage polarization and TLR4 as a downstream target. Diminishing miR-182 in MSC-Exo partially attenuated its modulation of macrophage polarization. Likewise, knock down of TLR4 also conferred cardioprotective efficacy and reduced inflammation level in a mouse model of myocardial ischemia/reperfusion. Conclusion: Our data indicates that MSC-Exo attenuates myocardial ischemia/reperfusion injury via shuttling miR-182 that modifies the polarization state of macrophages. This study sheds new light on the application of MSC-Exo a potential therapeutic tool for myocardial ischemia/reperfusion injury.
2021-09-01 | GSE120149 | GEO
Project description:The aim of this study was to compare miRNA expression in urinary exosomes from type 1 diabetic patients with and without incipient diabetic nephropathy. Overnight urine collections were obtained from normo- and microalbuminuric type 1 diabetic patients. Urines were pre-cleared by both centrifugation and filtration, urinary exosomes were isolated by two consecutive ultracentrifugation steps and total RNA extracted. Differential miRNA profiling was performed using a Human TaqMan miRNA Array A on an 7900HT Fast Real-Time PCR System. Results showed that expression of 22 urinary exosomal miRNAs differed in incipient diabetic nephropathy. Differential qPCR miRNA profiling was performed on urinary exosomes from 2 pairs of micro/normoalbuminuric type 1 diabetic patients comparable for age, sex, diabetes duration, and tightly matched for HbA1c (1° pair: 8.1 vs. 8.1, 2° pair: 8.7 vs. 8.7). MiRNAs were considered differentially expressed if they exhibited greater than twofold expression differences in both pairs.
2014-02-14 | E-GEOD-48318 | biostudies-arrayexpress
Project description:Stroke places a huge burden on society today, and great of studies were devoted for seeking safe and effective therapeutic strategy to improve the prognosis of stroke. Plasma exosome has exhibited its therapeutic potential against ischemia and reperfusion injury via ameliorating inflammation. To enhance therapeutic potential in patients with ischemic injury, we isolated exosomes from melatonin pretreated rat plasma and assessed the neurological protective effect in a rat model of focal cerebral ischemia. Treatment with melatonin enhanced plasma exosome therapeutic effect against ischemia induced inflammatory response and inflammasome mediated pyroptosis. In addition, we confirmed ischemic stroke induced pyroptotic cell death mainly occurred in microglia, while administration of melatonin treated exosome further effectively decreased infract volume and improved function recovery via regulation of TLR-4/NF-κB signaling pathway. Finally, the altered miRNAs profile in melatonin treated plasma exosomes demonstrated the regulatory mechanisms. This study suggests plasma exosome with melatonin pretreatment might be a more effective strategy for patients with ischemic brain injury. Further exploration of key molecules in plasma exosome may devote more therapeutic value for cerebral ischemic injury.
2020-03-27 | GSE147578 | GEO
Project description:miRNA profiling of urinary exosomes to assess the progression of acute kidney injury
| PRJNA515823 | ENA
Project description:miRNA profiling of urinary exosomes to assess the progression of acute kidney injury
| PRJNA513035 | ENA
Project description:This experiment was designed to identify changes in microRNA expression in patients with early or late stage ADPKD vs healthy controls. microRNA was isolated from urinary exosomes before high throughput sequencing. Expression levels was analysed using STRAND NGS software.
2021-01-01 | E-MTAB-8109 | biostudies-arrayexpress
Project description:Heart disease remains the leading cause of death globally. Although reperfusion following myocardial ischemia can prevent death by restoring nutrient flow, ischemia/reperfusion injury can cause significant heart damage. The mechanisms that drive ischemia/reperfusion injury are not well understood; currently, few methods can predict the state of the cardiac muscle cell and its metabolic conditions during ischemia. Here, we explored the energetic sustainability of cardiomyocytes, using a model for cellular metabolism to predict the levels of ATP following hypoxia. We modeled glycolytic metabolism with a system of coupled ordinary differential equations describing the individual metabolic reactions within the cardiomyocyte over time. Reduced oxygen levels and ATP consumption rates were simulated to characterize metabolite responses to ischemia. By tracking biochemical species within the cell, our model enables prediction of the cell’s condition up to the moment of reperfusion. The simulations revealed a distinct transition between energetically sustainable and unsustainable ATP concentrations for various energetic demands. Our model illustrates how even low oxygen concentrations allow the cell to perform essential functions. We found that the oxygen level required for a sustainable level of ATP increases roughly linearly with the ATP consumption rate. An extracellular O2 concentration of ~0.007 mM could supply basic energy needs in non-beating cardiomyocytes, suggesting that increased collateral circulation may provide an important source of oxygen to sustain the cardiomyocyte during extended ischemia. Our model provides a time-dependent framework for studying various intervention strategies to change the outcome of reperfusion.
2020-08-25 | BIOMD0000000961 | BioModels
Project description:The LAD of C57BL6 mice were temporally occluded to induce ischemia-reperfusion injury of the heart. Mice received a daily dose of the porcupine inhibitor LGK974 starting directly after the surgery to prevent Wnt protein secretion. Control animals received a DMSO vehicle control. Hearts were extracted 48h after induction of ischemia-reperfusion injury. The infarcted area was identified and processed for RNAseq analysis.
2022-11-02 | GSE185444 | GEO
Project description:The aim of this study was to compare miRNA expression in urinary exosomes from type 1 diabetic patients with and without incipient diabetic nephropathy. Overnight urine collections were obtained from normo- and microalbuminuric type 1 diabetic patients. Urines were pre-cleared by both centrifugation and filtration, urinary exosomes were isolated by two consecutive ultracentrifugation steps and total RNA extracted. Differential miRNA profiling was performed using a Human TaqMan miRNA Array A on an 7900HT Fast Real-Time PCR System. Results showed that expression of 22 urinary exosomal miRNAs differed in incipient diabetic nephropathy.
2014-02-14 | GSE48318 | GEO