Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis

Yajaira Suárez, Carlos Fernández-Hernando, Jun Yu, Scott A. Gerber, Kenneth D. Harrison, Jordan S. Pober, M. Luisa Iruela-Arispe, Matthias Merkenschlager, William C. Sessa

Research output: Contribution to journalArticlepeer-review

396 Scopus citations

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 upregulation 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.

Original languageEnglish (US)
Pages (from-to)14082-14087
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume105
Issue number37
DOIs
StatePublished - Sep 16 2008

Keywords

  • Endothelium
  • VEGF

ASJC Scopus subject areas

  • General

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