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Sci Rep. 2015 Feb 17;5:8505. doi: 10.1038/srep08505.

Inflammation-induced endothelial cell-derived extracellular vesicles modulate the cellular status of pericytes.

Author information

1
Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
2
Bio Bank Omics Unit, National Center for Geriatrics and Gerontology, Aichi, Japan.
3
1] Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan [2] Manufacturing &Engineering Lab., Astellas Pharma Inc., Tsukuba, Japan.
4
1] Toyama Prefectural Institute for Pharmaceutical Research, Toyama, Japan [2] Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
5
1] Bio Bank Omics Unit, National Center for Geriatrics and Gerontology, Aichi, Japan [2] Department of Cancer Genetics, Roswell Park Cancer Institute, Buffalo, NY, USA.
6
Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
7
Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
8
The Center for Graduate Medical Education, Jichi Medical University, Tochigi, Japan.
9
Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
10
Department of Emergency and Critical Care Medicine, Nagoya University, Nagoya, Japan.

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.

PMID:
25687367
PMCID:
PMC4330530
DOI:
10.1038/srep08505
[Indexed for MEDLINE]
Free PMC Article
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