Endothelial cells secrete exosomes containing miR-214, which suppress senescence and stimulates an angiogenic program in target cells.
Exosomal miR-214 regulates ataxia telangiectasia mutated expression in recipient endothelial cells.
Signaling between endothelial cells, endothelial progenitor cells, and stromal cells is crucial for the establishment and maintenance of vascular integrity and involves exosomes, among other signaling pathways. Exosomes are important mediators of intercellular communication in immune signaling, tumor survival, stress responses, and angiogenesis. The ability of exosomes to incorporate and transfer messenger RNAs (mRNAs) encoding for “acquired” proteins or micro RNAs (miRNAs) repressing “resident” mRNA translation suggests that they can influence the physiological behavior of recipient cells. We demonstrate that miR-214, an miRNA that controls endothelial cell function and angiogenesis, plays a dominant role in exosome-mediated signaling between endothelial cells. Endothelial cell–derived exosomes stimulated migration and angiogenesis in recipient cells, whereas exosomes from miR-214–depleted endothelial cells failed to stimulate these processes. Exosomes containing miR-214 repressed the expression of ataxia telangiectasia mutated in recipient cells, thereby preventing senescence and allowing blood vessel formation. Concordantly, specific reduction of miR-214 content in exosome-producing endothelial cells abolishes the angiogenesis stimulatory function of the resulting exosomes. Collectively, our data indicate that endothelial cells release miR-214–containing exosomes to stimulate angiogenesis through the silencing of ataxia telangiectasia mutated in neighboring target cells.
- Submitted February 5, 2013.
- Accepted March 6, 2013.
- © 2013 by The American Society of Hematology