Article
MicroRNA-147b Regulates Vascular Endothelial Barrier Function by Targeting ADAM15 Expression
PLOS ONE
(2014)
Abstract
A disintegrin and metalloproteinase15 (ADAM15) has been shown to be upregulated and mediate endothelial hyperpermeability during inflammation and sepsis. This molecule contains multiple functional domains with the ability to modulate diverse cellular processes including cell adhesion, extracellular matrix degradation, and ectodomain shedding of transmembrane proteins. These characteristics make ADAM15 an attractive therapeutic target in various diseases. The lack of pharmacological inhibitors specific to ADAM15 prompted our efforts to identify biological or molecular tools to alter its expression for further studying its function and therapeutic implications. The goal of this study was to determine if ADAM15-targeting microRNAs altered ADAM15-induced endothelial barrier dysfunction during septic challenge by bacterial lipopolysaccharide (LPS). An in silico analysis followed by luciferase reporter assay in human vascular endothelial cells identified miR-147b with the ability to target the 3′ UTR of ADAM15. Transfection with a miR-147b mimic led to decreased total, as well as cell surface expression of ADAM15 in endothelial cells, while miR-147b antagomir produced an opposite effect. Functionally, LPS-induced endothelial barrier dysfunction, evidenced by a reduction in transendothelial electric resistance and increase in albumin flux across endothelial monolayers, was attenuated in cells treated with miR-147b mimics. In contrast, miR-147b antagomir exerted a permeability-increasing effect in vascular endothelial cells similar to that caused by LPS. Taken together, these data suggest the potential role of miR147b in regulating endothelial barrier function by targeting ADAM15 expression.
Keywords
- transfection,
- endothelial cells,
- luciferase,
- albumins,
- untranslated regions,
- permeability
Disciplines
Publication Date
October 15, 2014
DOI
10.1371/journal.pone.0110286
Publisher Statement
For complete list of authors, please see article.
This document was originally published in PLOS ONE by The Public Library of Science (PLOS). This work is provided under a Creative Commons Attribution license. Details regarding the use of this work can be found at: http://creativecommons.org/licenses/by/4.0/. doi: 10.1371/journal.pone.0110286
Citation Information
Richard S. Beard. "MicroRNA-147b Regulates Vascular Endothelial Barrier Function by Targeting ADAM15 Expression" PLOS ONE Vol. 9 Iss. 10 (2014) p. e110286-1 - e110286-9 ISSN: 19326203 Available at: http://works.bepress.com/richard-beard/5/
Creative Commons license
This work is licensed under a Creative Commons CC_BY International License.