title: Inflammation-induced endothelial cell-derived extracellular vesicles modulate the cellular status of pericytes.
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.
authors: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Seiji
authors: S
authors: Yamamoto
authors: Bio Bank Omics Unit, National Center for Geriatrics and Gerontology, Aichi, Japan.
authors: Shumpei
authors: S
authors: Niida
authors: 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.
authors: Erika
authors: E
authors: Azuma
authors: 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.
authors: Tsutomu
authors: T
authors: Yanagibashi
authors: 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.
authors: Masashi
authors: M
authors: Muramatsu
authors: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Ting Ting
authors: TT
authors: Huang
authors: Medical Proteomics Laboratory, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
authors: Hiroshi
authors: H
authors: Sagara
authors: Bio Bank Omics Unit, National Center for Geriatrics and Gerontology, Aichi, Japan.
authors: Sayuri
authors: S
authors: Higaki
authors: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Masashi
authors: M
authors: Ikutani
authors: Department of Immunobiology and Pharmacological Genetics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Yoshinori
authors: Y
authors: Nagai
authors: 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.
authors: Kiyoshi
authors: K
authors: Takatsu
authors: The Center for Graduate Medical Education, Jichi Medical University, Tochigi, Japan.
authors: Kenji
authors: K
authors: Miyazaki
authors: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Takeru
authors: T
authors: Hamashima
authors: Department of Molecular Neuroscience, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Hisashi
authors: H
authors: Mori
authors: Department of Emergency and Critical Care Medicine, Nagoya University, Nagoya, Japan.
authors: Naoyuki
authors: N
authors: Matsuda
authors: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Yoko
authors: Y
authors: Ishii
authors: Department of Pathology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors: Masakiyo
authors: M
authors: Sasahara
mesh_terms: D000818:Animals; D002450:Cell Communication; D042783:Endothelial Cells / Q000378:metabolism*; D000067128:Extracellular Vesicles / Q000378:metabolism*; D020869:Gene Expression Profiling; D007249:Inflammation / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D020286:Pericytes / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger