title: Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis.
abstract: Posttranscriptional gene regulation by microRNAs (miRNAs) is important for many aspects of development, homeostasis, and disease. Here, we show that reduction of endothelial miRNAs by cell-specific inactivation of Dicer, the terminal endonuclease responsible for the generation of miRNAs, reduces postnatal angiogenic response to a variety of stimuli, including exogenous VEGF, tumors, limb ischemia, and wound healing. Furthermore, VEGF regulated the expression of several miRNAs, including the up-regulation of components of the c-Myc oncogenic cluster miR-17-92. Transfection of endothelial cells with components of the miR-17-92 cluster, induced by VEGF treatment, rescued the induced expression of thrombospondin-1 and the defect in endothelial cell proliferation and morphogenesis initiated by the loss of Dicer. Thus, endothelial miRNAs regulate postnatal angiogenesis and VEGF induces the expression of miRNAs implicated in the regulation of an integrated angiogenic response.
authors.affiliation: Department of Immunobiology, Vascular Biology and Therapeutics Program, Yale University School of Medicine, Amistad Research Building, New Haven, CT 06519, USA.
authors.forename: Yajaira
authors.initials: Y
authors.lastname: Suárez
authors.forename: Carlos
authors.initials: C
authors.lastname: Fernández-Hernando
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
authors.forename: Scott A
authors.initials: SA
authors.lastname: Gerber
authors.forename: Kenneth D
authors.initials: KD
authors.lastname: Harrison
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Pober
authors.forename: M Luisa
authors.initials: ML
authors.lastname: Iruela-Arispe
authors.forename: Matthias
authors.initials: M
authors.lastname: Merkenschlager
authors.forename: William C
authors.initials: WC
authors.lastname: Sessa
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D035683:MicroRNAs / Q000235:genetics*; D018919:Neovascularization, Physiologic; D043244:Ribonuclease III; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology
chemical_list: D035683:MicroRNAs; D042461:Vascular Endothelial Growth Factor A; D004722:Endoribonucleases; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases
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