MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.

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...

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Autores principales:	Victor Chatterjee, Richard S Beard, Jason J Reynolds, Ricci Haines, Mingzhang Guo, Matthew Rubin, Jenny Guido, Mack H Wu, Sarah Y Yuan
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2194224247ca49149c58ceba9e334dd0
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spelling	oai:doaj.org-article:2194224247ca49149c58ceba9e334dd02021-11-25T05:56:27ZMicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.1932-620310.1371/journal.pone.0110286https://doaj.org/article/2194224247ca49149c58ceba9e334dd02014-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0110286https://doaj.org/toc/1932-6203A 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.Victor ChatterjeeRichard S BeardJason J ReynoldsRicci HainesMingzhang GuoMatthew RubinJenny GuidoMack H WuSarah Y YuanPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 10, p e110286 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Victor Chatterjee Richard S Beard Jason J Reynolds Ricci Haines Mingzhang Guo Matthew Rubin Jenny Guido Mack H Wu Sarah Y Yuan MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.
description	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.
format	article
author	Victor Chatterjee Richard S Beard Jason J Reynolds Ricci Haines Mingzhang Guo Matthew Rubin Jenny Guido Mack H Wu Sarah Y Yuan
author_facet	Victor Chatterjee Richard S Beard Jason J Reynolds Ricci Haines Mingzhang Guo Matthew Rubin Jenny Guido Mack H Wu Sarah Y Yuan
author_sort	Victor Chatterjee
title	MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.
title_short	MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.
title_full	MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.
title_fullStr	MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.
title_full_unstemmed	MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.
title_sort	microrna-147b regulates vascular endothelial barrier function by targeting adam15 expression.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/2194224247ca49149c58ceba9e334dd0
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MicroRNA-147b regulates vascular endothelial barrier function by targeting ADAM15 expression.

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