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 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-alpha-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.
Harris
Tamia A
TA
Cellular and Molecular Medicine Program and Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Yamakuchi
Munekazu
M
Ferlito
Marcella
M
Mendell
Joshua T
JT
Lowenstein
Charles J
CJ
D001483:Base Sequence; D002448:Cell Adhesion / Q000235:genetics; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D016372:RNA, Antisense / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics*
C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D016372:RNA, Antisense; D019010:Vascular Cell Adhesion Molecule-1