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

被引:877
作者
Harris, Tamia A. [2 ]
Yamakuchi, Munekazu [1 ]
Ferlito, Marcella [1 ]
Mendell, Joshua T. [3 ,5 ,6 ]
Lowenstein, Charles J. [1 ,2 ,4 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA
[2] Johns Hopkins Univ, Sch Med, Cellular & Mol Med Program, Baltimore, MD 21205 USA
[3] Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21205 USA
[4] Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
[5] Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA
[6] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA
关键词
inflammation; nitric oxide; leukocyte; atherosclerosis;
D O I
10.1073/pnas.0707493105
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:1516 / 1521
页数:6
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