Abstract
Emerging lines of evidence have shown that extracellular vesicles (EVs) mediate cell-to-cell communication by exporting encapsulated materials, such as microRNAs (miRNAs), to target cells. Endothelial cell-derived EVs (E-EVs) are upregulated in circulating blood in different pathological conditions; however, the characteristics and the role of these E-EVs are not yet well understood. In vitro studies were conducted to determine the role of inflammation-induced E-EVs in the cell-to-cell communication between vascular endothelial cells and pericytes/vSMCs. Stimulation with inflammatory cytokines and endotoxin immediately induced release of shedding type E-EVs from the vascular endothelial cells, and flow cytometry showed that the induction was dose dependent. MiRNA array analyses revealed that group of miRNAs were specifically increased in the inflammation-induced E-EVs. E-EVs added to the culture media of cerebrovascular pericytes were incorporated into the cells. The E-EV-supplemented cells showed highly induced mRNA and protein expression of VEGF-B, which was assumed to be a downstream target of the miRNA that was increased within the E-EVs after inflammatory stimulation. The results suggest that E-EVs mediate inflammation-induced endothelial cell-pericyte/vSMC communication, and the miRNAs encapsulated within the E-EVs may play a role in regulating target cell function. E-EVs may be new therapeutic targets for the treatment of inflammatory diseases.
Highlights
Emerging lines of evidence have shown that extracellular vesicles (EVs) mediate cell-to-cell communication by exporting encapsulated materials, such as microRNAs, to target cells
The Endothelial cell-derived EVs (E-EVs)-supplemented cells showed highly induced mRNA and protein expression of VEGF-B, which was assumed to be a downstream target of the miRNA that was increased within the E-EVs after inflammatory stimulation
Some of the membranelocalized EGFP (M-EGFP)-positive E-EVs were localized near the nucleus, as confirmed by the Y-Z cross-sectional image and single-plane sequential Z images (Fig. 4, upper right and bottom row). These findings suggest that the bioactive molecules encapsulated in the E-EVs were transferred into human brain pericytes (HBPCs)
Summary
Emerging lines of evidence have shown that extracellular vesicles (EVs) mediate cell-to-cell communication by exporting encapsulated materials, such as microRNAs (miRNAs), to target cells. The results suggest that E-EVs mediate inflammation-induced endothelial cell-pericyte/vSMC communication, and the miRNAs encapsulated within the E-EVs may play a role in regulating target cell function. Cell-to-cell communication is mediated by secreted bioactive molecules, such as short form peptides, proteins, lipids, and nucleic acids These small molecules are commonly released by cells and bind to specific receptors on target cells, which induces intracellular signaling and changes the target cell’s pathophysiological state. The inflammation-related miRNAs, miR-101, miR-144, and miR-155, were reported to modulate protein biogenesis in lung epithelial and endothelial cells[20,21] These miRNAs can be carried by E-EVs; their roles in EEV-mediated cell-to-cell communication are not yet known
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