Cellular stress conditions are reflected in the protein and RNA content of endothelial cell-derived exosomes

By Olivier G. de Jong, M. Verhaar, Yong Chen, P. Vader, H. Gremmels, G. Posthuma, Raymond Schiffelers, Marjan Gucek, B. W. van Balkom. Journal of Extracellular Vesicles, 2012

605 citations recorded by the source corpus.

Background: The healthy vascular endothelium, which forms the barrier between blood and the surrounding tissues, is known to efficiently respond to stress signals like hypoxia and inflammation by adaptation of cellular physiology and the secretion of (soluble) growth factors and cytokines. Exosomes are potent mediators of intercellular communication. Their content consists of RNA and proteins from the cell of origin, and thus depends on the condition of these cells at the time of exosome biogenesis. It has been suggested that exosomes protect their target cells from cellular stress through the transfer of RNA and proteins. We hypothesized that endothelium-derived exosomes are involved in the endothelial response to cellular stress, and that exosome RNA and protein content reflect the effects of cellular stress induced by hypoxia, inflammation or hyperglycemia. Methods: We exposed cultured endothelial cells to different types of cellular stress (hypoxia, TNF-α-induced activation, high glucose and mannose concentrations) and compared mRNA and protein content of exosomes produced by these cells by microarray analysis and a quantitative proteomics approach. Results: We identified 1,354 proteins and 1,992 mRNAs in endothelial cell-derived exosomes. Several proteins and mRNAs showed altered abundances after exposure of their producing cells to cellular stress, which were confirmed by immunoblot or qPCR analysis. Conclusion: Our data show that hypoxia and endothelial activation are reflected in RNA and protein exosome composition, and that exposure to high sugar concentrations alters exosome protein composition only to a minor extend, and does not affect exosome RNA composition. To access the supplementary material to this article: Tables SI-SIV and Figures S1-2, please see Supplementary files under Article Tools online.

Subfields: Cancer Research, Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/24bccc44cbb079532d76a2cb2cfa467c22ad7cac

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Cancer Research

In Cell Biology

In Molecular Biology

Citations in the corpus

Introduction to Extracellular Vesicles: Biogenesis, RNA Cargo Selection, Content, Release, and Uptake (2016, neutral): “Conversely, overexpression of a miRNA enriches it in EVs (de Jong et al. 2012; Squadrito et al. 2014).”
Diabetic cardiomyopathy: a hyperglycaemia- and insulin-resistance-induced heart disease (2017, neutral): “RNA content in endothelial cell-derived exosomes [40, 41].”
Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. (2014, background): “For instance, inflammatory signals (e.g., LPS, TNFα, IFNγ) strongly affect the protein and/or RNA composition of EVs released by dendritic (Segura et al. 2005), endothelial (de Jong et al. 2012), or mesenchymal stem cells (Kilpinen et al. 2013).”
SORTING IT OUT: REGULATION OF EXOSOME LOADING (2014, background): “Exosome-mediated signaling in tumors is thus affected by a variety of stress conditions [111], and promotes tumor progression through communication between the tumor and surrounding stromal tissue, activation of proliferative and angiogenic pathways, promotion of immune suppression, and initiation o”
Biological properties of extracellular vesicles and their physiological functions (2015, background): “EC stress influenced the protein and RNA content of ECderived EV, which would interact with macrophages in vascular niches to promote vascular growth (379,380).”