Genome-wide Profiling of Urinary Extracellular Vesicle microRNAs Associated With Diabetic Nephropathy in Type 1 Diabetes
Vikas GhaiXiaogang WuAnjalei Bheda-MalgeChristos ArgyropoulosJosé F. BernardoTrevor J. OrchardDavid J. GalasKai Wang
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IntroductionDiabetic nephropathy (DN) is a form of progressive kidney disease that often leads to end-stage renal disease (ESRD). It is initiated by microvascular complications due to diabetes. Although microalbuminuria (MA) is the earliest clinical indication of DN among patients with type 1 diabetes (T1D), it lacks the sensitivity and specificity to detect the early onset of DN. Recently, microRNAs (miRNAs) have emerged as critical regulators in diabetes as well as various forms of kidney disease, including renal fibrosis, acute kidney injury, and progressive kidney disease. Additionally, circulating extracellular miRNAs, especially miRNAs packaged in extracellular vesicles (EVs), have garnered significant attention as potential noninvasive biomarkers for various diseases and health conditions.MethodsAs part of the University of Pittsburgh Epidemiology of Diabetes Complications (EDC) study, urine was collected from individuals with T1D with various grades of DN or MA (normal, overt, intermittent, and persistent) over a decade at prespecified intervals. We isolated EVs from urine and analyzed the small-RNA using NextGen sequencing.ResultsWe identified a set of miRNAs that are enriched in urinary EVs compared with EV-depleted samples, and identified a number of miRNAs showing concentration changes associated with DN occurrence, MA status, and other variables, such as hemoglobin A1c levels.ConclusionMany of the miRNAs associated with DN occurrence or MA status directly target pathways associated with renal fibrosis (including transforming growth factor-β and phosphatase and tensin homolog), which is one of the major contributors to the pathology of DN. These miRNAs are potential biomarkers for DN and MA.Keywords:
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Other SectionsABSTRACTINTRODUCTIONEXTRACELLULAR VESICLE DERIVED FROM STEM CELLSIMPROVEMENT OF EXTRACELLULAR VESICLEREGENERATIVE MEDICINE FOR TISSUE REPAIRCONCLUSIONACKNOWLEDGEMENTSCONFLICTS OF INTERESTFIGURETABLESREFERENCES
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Extracellular vesicle‐mediated delivery of circDYM alleviates CUS‐induced depressive‐like behaviours
Abstract Major depressive disorder (MDD) is the most prevalent psychiatric disorder worldwide and severely limits psychosocial function and quality of life, but no effective medication is currently available. Circular RNAs (circRNAs) have been revealed to participate in the MDD pathological process. Targeted delivery of circRNAs without blood‐brain barrier (BBB) restriction for remission of MDD represents a promising approach for antidepressant therapy. In this study, RVG‐circDYM‐extracellular vesicles (RVG‐circDYM‐EVs) were engineered to target and preferentially transfer circDYM to the brain, and the effect on the pathological process in a chronic unpredictable stress (CUS) mouse model of depression was investigated. The results showed that RVG‐circDYM‐EVs were successfully purified by ultracentrifugation from overexpressed circDYM HEK 293T cells, and the characterization of RVG‐circDYM‐EVs was successfully demonstrated in terms of size, morphology and specific markers. Beyond demonstrating proof‐of‐concept for an RNA drug delivery technology, we observed that systemic administration of RVG‐circDYM‐EVs efficiently delivered circDYM to the brain, and alleviated CUS‐induced depressive‐like behaviours, and we discovered that RVG‐circDYM‐EVs notably inhibited microglial activation, BBB leakiness and peripheral immune cells infiltration, and attenuated astrocyte disfunction induced by CUS. CircDYM can bind mechanistically to the transcription factor TAF1 (TATA‐box binding protein associated factor 1), resulting in the decreased expression of its downstream target genes with consequently suppressed neuroinflammation. Taken together, our findings suggest that extracellular vesicle‐mediated delivery of circDYM is effective for MDD treatment and promising for clinical applications.
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Abstract The “QuantitatEVs: multiscale analyses, from bulk to single vesicle” workshop aimed to discuss quantitative strategies and harmonized wet and computational approaches toward the comprehensive analysis of extracellular vesicles (EVs) from bulk to single vesicle analyses with a special focus on emerging technologies. The workshop covered the key issues in the quantitative analysis of different EV‐associated molecular components and EV biophysical features, which are considered the core of EV‐associated biomarker discovery and validation for their clinical translation. The in‐person‐only workshop was held in Trento, Italy, from January 31 st to February 2 nd , 2023, and continued in Milan on February 3 rd with “Next Generation EVs,” a satellite event dedicated to early career researchers (ECR). This report summarizes the main topics and outcomes of the workshop.
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Liquid biopsy-derived extracellular vesicles (EVs) are an auspicious source for transcriptomic biomarker studies. Here, we review the potential of EV microRNAs (miRNAs) biomarkers, exemplary outline commonly used methods to elucidate new biomarker signatures, and pivotally discuss their applicability at present. Keywords: extracellular vesicles, liquid biopsies, transcriptomic biomarkers, microRNAs
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Extracellular Vesicles In article number 2304926, Chi-An Cheng and co-workers develop an innovative framework for decoding the spatial distribution of extracellular vesicle (EV) protein biomarkers, offering unparalleled sensitivity and specificity. This innovation provides a solution for the precise quantification of EV protein concentrations in plasma, revolutionizing EV research and showcasing its clinical diagnostic potential.
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Other SectionsABSTRACTINTRODUCTIONADVANTAGES OF STEM CELL-DERIVED EXTRACELLULAR VESICLES OVER OTHER THERAPEUTIC STRATEGIESAPPLICATIONS OF EXTRACELLULAR VESICLES IN BRAIN DISEASESLIMITATIONS OF CURRENT MSC-EV THERAPEUTICSENHANCING THE EFFICACY OF THERAPEUTIC EXTRACELLULAR VESICLESCLINICAL SCALE PRODUCTION OF EXTRACELLULAR VESICLESCONCLUSIONSACKNOWLEDGEMENTSCONFLICTS OF INTERESTFIGURESTABLEREFERENCES
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