Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 30, Issue 10, Pages 1990-U234Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/ATVBAHA.110.211706
Keywords
endothelium; gene expression; immune system; vascular biology; microRNA
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Funding
- National Institutes of Health [R01-HL63706-04, R01-HL074061, P01-HL65608, P01-HL56091, R01-HL082717]
- American Heart Association [0140210N, SDG 0835446N]
- Paul Yu Professorship
- Cellular and Molecular Medicine Program
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Objective-MicroRNA plays important roles in vascular biology, but the regulation of endothelial-specific microRNA is not well characterized. MicroRNA-126 (miR-126) is highly expressed in endothelial cells, and it regulates angiogenesis and vascular inflammation. Here we show that the transcription factors Ets-1 and Ets-2 regulate miR-126 expression. Methods and Results-A genomic region between -71 and -100 bp upstream of the miR-126 transcriptional start site is critical for transactivation of the gene containing miR-126. This genomic region contains a potential Ets binding site. Mutations within the Ets binding site block transactivation, and Ets-1 and Ets-2 interact with this critical genomic region. Knockdown of endogenous Ets-1 and Ets-2 decreases miR-126 expression. Finally, knockdown of miR-126 alters regulation of an Ets-1 target gene. Conclusion-Taken together, these data show that the transcription factors Ets-1 and Ets-2 play a key role in controlling the expression of miR-126 and suggest that miR-126 may mediate some of their vascular effects. (Arterioscler Thromb Vasc Biol. 2010; 30:1990-1997.)
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