Exosome-delivered microRNAs modulate the inflammatory response to endotoxin

Alexander, Margaret; Hu, Ruiming; Runtsch, Marah C.; Kagele, Dominique; Mosbruger, Timothy; Tolmachova, Tanya; Seabra, Miguel C.; Round, June L.; Ward, Diane M.; O’Connell, Ryan M.

doi:10.1038/ncomms8321

Cited by 602 publications

(568 citation statements)

References 46 publications

(84 reference statements)

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“…For most kits, variability of particle diameters was greater in sepsis samples, indicating disease-specific changes in circulating vesicles, or interferences caused by matrix effects in serum from critically ill patients. It is also conceivable that an increased proportion of immune cell-derived EVs or bacterial outer membrane vesicles, typically ranging from 20 to 300 nm in diameter, might contribute to the broader range of particles recovered from septic sera [70,71]. …”

Section: Discussionmentioning

confidence: 99%

Evaluation of serum extracellular vesicle isolation methods for profiling miRNAs by next‐generation sequencing

Buschmann

Kirchner

Hermann

et al. 2018

J of Extracellular Vesicle

189

149

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Extracellular vesicles (EVs) are intercellular communicators with key functions in physiological and pathological processes and have recently garnered interest because of their diagnostic and therapeutic potential. The past decade has brought about the development and commercialization of a wide array of methods to isolate EVs from serum. Which subpopulations of EVs are captured strongly depends on the isolation method, which in turn determines how suitable resulting samples are for various downstream applications. To help clinicians and scientists choose the most appropriate approach for their experiments, isolation methods need to be comparatively characterized. Few attempts have been made to comprehensively analyse vesicular microRNAs (miRNAs) in patient biofluids for biomarker studies. To address this discrepancy, we set out to benchmark the performance of several isolation principles for serum EVs in healthy individuals and critically ill patients. Here, we compared five different methods of EV isolation in combination with two RNA extraction methods regarding their suitability for biomarker discovery-focused miRNA sequencing as well as biological characteristics of captured vesicles. Our findings reveal striking method-specific differences in both the properties of isolated vesicles and the ability of associated miRNAs to serve in biomarker research. While isolation by precipitation and membrane affinity was highly suitable for miRNA-based biomarker discovery, methods based on size-exclusion chromatography failed to separate patients from healthy volunteers. Isolated vesicles differed in size, quantity, purity and composition, indicating that each method captured distinctive populations of EVs as well as additional contaminants. Even though the focus of this work was on transcriptomic profiling of EV-miRNAs, our insights also apply to additional areas of research. We provide guidance for navigating the multitude of EV isolation methods available today and help researchers and clinicians make an informed choice about which strategy to use for experiments involving critically ill patients.

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Section: Discussionmentioning

confidence: 99%

Evaluation of serum extracellular vesicle isolation methods for profiling miRNAs by next‐generation sequencing

Buschmann

Kirchner

Hermann

et al. 2018

J of Extracellular Vesicle

189

149

View full text Add to dashboard Cite

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“…Upon being released from cells, exosomes can distribute in biological fluids and be up‐taken by the same or a different type of cells, which then interact with exosomes and present biological functions 6. Previous studies showed that DC‐derived exosomes (DC‐exos) can exert biological effects via membrane proteins or inner contained miRNAs 7, 8, 9. Here, in the present study, we aimed at investigating whether DC‐exos are involved in endothelial inflammation and atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway

Gao

Yuan

et al. 2016

J Cellular Molecular Medi

205

137

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Whether dendritic cell (DC) derived exosomes play a role in the progression of endothelial inflammation and atherosclerosis remains unclear. Using a transwell system and exosome release inhibitor GW4869, we demonstrated that mature DCs contributed to endothelial inflammation and exosomes were involved in the process. To further confirm this finding, we isolated exosomes from bone marrow dendritic cell (BMDC) culture medium (named DC‐exos) and stimulated human umbilical vein endothelial cell (HUVEC) with these DC‐exos. We observed that mature DC‐exos increased HUVEC inflammation through NF‐κB pathway in a manner similar to that of lipopolysaccharide. After a protein array analysis of exosomes, we identified and confirmed tumour necrosis factor (TNF)‐α on exosome membrane being the trigger of NF‐κB pathway in HUVECs. We then performed an in vivo study and found that the aorta endothelial of mice could uptake intravenously injected exosomes and was activated by these exosomes. After a period of 12 weeks of mature DC‐exos injection into ApoE−/− mice, the atherosclerotic lesions significantly increased. Our study demonstrates that mature DCs derived exosomes increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway. This finding extends our knowledge on how DCs affect inflammation and provides a potential method to prevent endothelial inflammation and atherosclerosis.

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“…The capture of EVs by target cells is involved in a broad range of biological processes including: angiogenesis [11], bone development [12], interneuronal communication [13], cell migration [14] and inflammation regulation [15]. Mechanisms for these processes are diverse but generally relate to the delivery of bioactive RNA, protein, metabolite and/or lipid cargoes.…”

Section: Introductionmentioning

confidence: 99%

Glycosylation of extracellular vesicles: current knowledge, tools and clinical perspectives

Williams

Royo

Aizpurua‐Olaizola

et al. 2018

J of Extracellular Vesicle

181

140

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It is now acknowledged that extracellular vesicles (EVs) are important effectors in a vast number of biological processes through intercellular transfer of biomolecules. Increasing research efforts in the EV field have yielded an appreciation for the potential role of glycans in EV function. Indeed, recent reports show that the presence of glycoconjugates is involved in EV biogenesis, in cellular recognition and in the efficient uptake of EVs by recipient cells. It is clear that a full understanding of EV biology will require researchers to focus also on EV glycosylation through glycomics approaches. This review outlines the major glycomics techniques that have been applied to EVs in the context of the recent findings. Beyond understanding the mechanisms by which EVs mediate their physiological functions, glycosylation also provides opportunities by which to engineer EVs for therapeutic and diagnostic purposes. Studies characterising the glycan composition of EVs have highlighted glycome changes in various disease states, thus indicating potential for EV glycans as diagnostic markers. Meanwhile, glycans have been targeted as molecular handles for affinity-based isolation in both research and clinical contexts. An overview of current strategies to exploit EV glycosylation and a discussion of the implications of recent findings for the burgeoning EV industry follows the below review of glycomics and its application to EV biology.

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Exosome-delivered microRNAs modulate the inflammatory response to endotoxin

Cited by 602 publications

References 46 publications

Evaluation of serum extracellular vesicle isolation methods for profiling miRNAs by next‐generation sequencing

Evaluation of serum extracellular vesicle isolation methods for profiling miRNAs by next‐generation sequencing

Exosomes derived from mature dendritic cells increase endothelial inflammation and atherosclerosis via membrane TNF‐α mediated NF‐κB pathway

Glycosylation of extracellular vesicles: current knowledge, tools and clinical perspectives

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