TY - JOUR
T1 - Dicer-dependent endothelial microRNAs are necessary for postnatal angiogenesis
AU - Suárez, Yajaira
AU - Fernández-Hernando, Carlos
AU - Yu, Jun
AU - Gerber, Scott A.
AU - Harrison, Kenneth D.
AU - Pober, Jordan S.
AU - Iruela-Arispe, M. Luisa
AU - Merkenschlager, Matthias
AU - Sessa, William C.
PY - 2008/9/16
Y1 - 2008/9/16
N2 - 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.
AB - 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.
KW - Endothelium
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=52949090784&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=52949090784&partnerID=8YFLogxK
U2 - 10.1073/pnas.0804597105
DO - 10.1073/pnas.0804597105
M3 - Article
C2 - 18779589
AN - SCOPUS:52949090784
SN - 0027-8424
VL - 105
SP - 14082
EP - 14087
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 37
ER -