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

Publication Type	Academic Article
Authors	Saxena A, Walters M, Shieh J, Shen L, Gomi K, Downey R, Crystal R, Moore M
Journal	Sci Rep
Volume	11
Issue	1
Pagination	6104
Date Published	03/17/2021
ISSN	2045-2322
Keywords	Endothelial Cells, Extracellular Vesicles, MAP Kinase Signaling System, Tobacco Products, Tobacco Smoke Pollution
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.
DOI	10.1038/s41598-021-85534-6
PubMed ID	33731767
PubMed Central ID	PMC7969738