MicroRNA-126 regulates endothelial expression of vascular cell adhesion molecule 1

Adhesion molecules expressed by activated endothelial cells play a key role in regulating leukocyte trafficking to sites of inflammation. Resting endothelial cells normally do not express adhesion molecules, but cytokines activate endothelial cells to express adhesion molecules such as vascular cell...

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Published in:	Proceedings of the National Academy of Sciences - PNAS Vol. 105; no. 5; pp. 1516 - 1521
Main Authors:	Harris, Tamia A, Yamakuchi, Munekazu, Ferlito, Marcella, Mendell, Joshua T, Lowenstein, Charles J
Format:	Journal Article
Language:	English
Published:	United States National Academy of Sciences 05-02-2008 National Acad Sciences
Subjects:	Base Sequence Biological Sciences Cell adhesion & migration Cell Adhesion - genetics Cells Down-Regulation Endothelial cells Endothelium, Vascular - drug effects Endothelium, Vascular - metabolism Gene expression Gene Expression Regulation HEK293 cells Human umbilical vein endothelial cells Humans Leukocytes Leukocytes - immunology Messenger RNA MicroRNA MicroRNAs - antagonists & inhibitors MicroRNAs - genetics MicroRNAs - physiology Molecules Oligonucleotides RNA RNA, Antisense - pharmacology Vascular Cell Adhesion Molecule-1 - genetics
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Summary:	Adhesion molecules expressed by activated endothelial cells play a key role in regulating leukocyte trafficking to sites of inflammation. Resting endothelial cells normally do not express adhesion molecules, but cytokines activate endothelial cells to express adhesion molecules such as vascular cell adhesion molecule 1 (VCAM-1), which mediate leukocyte adherence to endothelial cells. We now show that endothelial cells express microRNA 126 (miR-126), which inhibits VCAM-1 expression. Transfection of endothelial cells with an oligonucleotide that decreases miR-126 permits an increase in TNF-α-stimulated VCAM-1 expression. Conversely, overexpression of the precursor to miR-126 increases miR-126 levels and decreases VCAM-1 expression. Additionally, decreasing endogenous miR-126 levels increases leukocyte adherence to endothelial cells. These data suggest that microRNA can regulate adhesion molecule expression and may provide additional control of vascular inflammation.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Edited by Richard A. Flavell, Yale University School of Medicine, New Haven, CT, and approved December 12, 2007 Author contributions: T.A.H., J.T.M., and C.J.L. designed research; T.A.H., M.Y., and M.F. performed research; T.A.H., J.T.M., and C.J.L. analyzed data; and T.A.H. and C.J.L. wrote the paper.
ISSN:	0027-8424 1091-6490
DOI:	10.1073/pnas.0707493105