Extracellular vesicles from human airway basal cells respond to cigarette smoke extract and affect vascular endothelial cells Journal Article


Authors: Saxena, A.; Walters, M. S.; Shieh, J. H.; Shen, L. B.; Gomi, K.; Downey, R. J.; Crystal, R. G.; Moore, M. A. S.
Article Title: Extracellular vesicles from human airway basal cells respond to cigarette smoke extract and affect vascular endothelial cells
Abstract: The human airway epithelium lining the bronchial tree contains basal cells that proliferate, differentiate, and communicate with other components of their microenvironment. One method that cells use for intercellular communication involves the secretion of exosomes and other extracellular vesicles (EVs). We isolated exosome-enriched EVs that were produced from an immortalized human airway basal cell line (BCi-NS1.1) and found that their secretion is increased by exposure to cigarette smoke extract, suggesting that this stress stimulates release of EVs which could affect signaling to other cells. We have previously shown that primary human airway basal cells secrete vascular endothelial growth factor A (VEGFA) which can activate MAPK signaling cascades in endothelial cells via VEGF receptor–2 (VEGFR2). Here, we show that exposure of endothelial cells to exosome-enriched airway basal cell EVs promotes the survival of these cells and that this effect also involves VEGFR2 activation and is, at least in part, mediated by VEGFA present in the EVs. These observations demonstrate that EVs are involved in the intercellular signaling between airway basal cells and the endothelium which we previously reported. The downstream signaling pathways involved may be distinct and specific to the EVs, however, as increased phosphorylation of Akt, STAT3, p44/42 MAPK, and p38 MAPK was not seen following exposure of endothelial cells to airway basal cell EVs. © 2021, The Author(s).
Journal Title: Scientific Reports
Volume: 11
ISSN: 2045-2322
Publisher: Nature Publishing Group  
Date Published: 2021-03-17
Start Page: 6104
Language: English
DOI: 10.1038/s41598-021-85534-6
PROVIDER: scopus
PMCID: PMC7969738
PUBMED: 33731767
DOI/URL:
Notes: Article -- Export Date: 1 April 2021 -- Source: Scopus
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MSK Authors
  1. Jae-Hung Shieh
    76 Shieh
  2. Robert J Downey
    254 Downey
  3. Malcolm A S Moore
    549 Moore
  4. Ashish Saxena
    7 Saxena
  5. Ling-Bo Shen
    13 Shen