Harris Tamia A, Yamakuchi Munekazu, Ferlito Marcella, Mendell Joshua T, Lowenstein Charles J
Cellular and Molecular Medicine Program and Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1516-21. doi: 10.1073/pnas.0707493105. Epub 2008 Jan 28.
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.
活化的内皮细胞所表达的黏附分子在调节白细胞向炎症部位的迁移中起关键作用。静息内皮细胞通常不表达黏附分子,但细胞因子可激活内皮细胞,使其表达诸如血管细胞黏附分子1(VCAM - 1)等黏附分子,这些分子介导白细胞与内皮细胞的黏附。我们现在发现内皮细胞表达微小RNA 126(miR - 126),它可抑制VCAM - 1的表达。用降低miR - 126的寡核苷酸转染内皮细胞,可使肿瘤坏死因子α刺激的VCAM - 1表达增加。相反,miR - 126前体的过表达会提高miR - 126水平并降低VCAM - 1表达。此外,降低内源性miR - 126水平会增加白细胞与内皮细胞的黏附。这些数据表明微小RNA可调节黏附分子的表达,并可能为血管炎症提供额外的调控机制。