![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Vol. 17, Issue 12, 5163-5172, December 2006
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
,||,¶,||,¶
*Obstetrics and Gynecology, Genetics and Development, Pathology, and ¶Institute of Cancer Genetics, Columbia University Medical Center, New York, NY 10032; Department of Cell and Developmental Biology, Weill Medical College of Cornell University, New York, NY 10021; and ||Strang Cancer Research Laboratory at The Rockefeller University, New York, NY 10021
Submitted April 20, 2006;
Revised September 18, 2006;
Accepted September 29, 2006
Monitoring Editor: Mark Ginsberg
Wnts are lipid-modified secreted glycoproteins that regulate diverse biological processes. We report that Wnt5a, which functions in noncanonical Wnt signaling, has activity on endothelial cells. Wnt5a is endogenously expressed in human primary endothelial cells and is expressed in murine vasculature at several sites in mouse embryos and tissues. Expression of exogenous Wnt5a in human endothelial cells promoted angiogenesis. Wnt5a induced noncanonical Wnt signaling in endothelial cells, as measured by Dishevelled and ERK1/2 phosphorylation, and inhibition of canonical Wnt signaling, a known property of Wnt5a. Wnt5a induced endothelial cell proliferation and enhanced cell survival under serum-deprived conditions. The Wnt5a-mediated proliferation was blocked by Frizzled-4 extracellular domain. Wnt5a expression enhanced capillary-like network formation, whereas reduction of Wnt5a expression decreased network formation. Reduced Wnt5a expression inhibited endothelial cell migration. Screening for Wnt5a-regulated genes in cultured endothelial cells identified several encoding angiogenic regulators, including matrix metalloproteinase-1, an interstitial collagenase, and Tie-2, a receptor for angiopoietins. Thus, Wnt5a acts through noncanonical Wnt signaling to promote angiogenesis.
Address correspondence to: Jan Kitajewski (jkk9{at}columbia.edu)
This article has been cited by other articles:
|
|
 |
|
  L. S. Barcelos, C. Duplaa, N. Krankel, G. Graiani, G. Invernici, R. Katare, M. Siragusa, M. Meloni, I. Campesi, M. Monica, et al. Human CD133+ Progenitor Cells Promote the Healing of Diabetic Ischemic Ulcers by Paracrine Stimulation of Angiogenesis and Activation of Wnt Signaling Circ. Res., May 8, 2009; 104(9): 1095 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Hayashi, D. W. Erikson, S. A. Tilford, B. M. Bany, J. A. Maclean II, E. B. Rucker III, G. A. Johnson, and T. E. Spencer Wnt Genes in the Mouse Uterus: Potential Regulation of Implantation Biol Reprod, May 1, 2009; 80(5): 989 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D.-H. Yang, J.-Y. Yoon, S.-H. Lee, V. Bryja, E. R. Andersson, E. Arenas, Y.-G. Kwon, and K.-Y. Choi Wnt5a Is Required for Endothelial Differentiation of Embryonic Stem Cells and Vascularization via Pathways Involving Both Wnt/{beta}-Catenin and Protein Kinase C{alpha} Circ. Res., February 13, 2009; 104(3): 372 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. F. Schafer, U. F. O. Luhmann, S. Feil, and W. Berger Differential Gene Expression in Ndph-Knockout Mice in Retinal Development Invest. Ophthalmol. Vis. Sci., February 1, 2009; 50(2): 906 - 916. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Daneman, D. Agalliu, L. Zhou, F. Kuhnert, C. J. Kuo, and B. A. Barres Wnt/{beta}-catenin signaling is required for CNS, but not non-CNS, angiogenesis PNAS, January 13, 2009; 106(2): 641 - 646. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Stenman, J. Rajagopal, T. J. Carroll, M. Ishibashi, J. McMahon, and A. P. McMahon Canonical Wnt Signaling Regulates Organ-Specific Assembly and Differentiation of CNS Vasculature Science, November 21, 2008; 322(5905): 1247 - 1250. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Nomachi, M. Nishita, D. Inaba, M. Enomoto, M. Hamasaki, and Y. Minami Receptor Tyrosine Kinase Ror2 Mediates Wnt5a-induced Polarized Cell Migration by Activating c-Jun N-terminal Kinase via Actin-binding Protein Filamin A J. Biol. Chem., October 10, 2008; 283(41): 27973 - 27981. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Loscertales, A. J. Mikels, J. K.-H. Hu, P. K. Donahoe, and D. J. Roberts Chick pulmonary Wnt5a directs airway and vascular tubulogenesis Development, April 1, 2008; 135(7): 1365 - 1376. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. George Wnt Pathway: A New Role in Regulation of Inflammation Arterioscler. Thromb. Vasc. Biol., March 1, 2008; 28(3): 400 - 402. [Full Text] [PDF]
|
|
|
|
|
|
E. D. Cohen, Y. Tian, and E. E. Morrisey Wnt signaling: an essential regulator of cardiovascular differentiation, morphogenesis and progenitor self-renewal Development, March 1, 2008; 135(5): 789 - 798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P.A. van Montfoort, J. P.M. Geraedts, J. C.M. Dumoulin, A. P.M. Stassen, J. L.H. Evers, and T. A.Y. Ayoubi Differential gene expression in cumulus cells as a prognostic indicator of embryo viability: a microarray analysis Mol. Hum. Reprod., March 1, 2008; 14(3): 157 - 168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Ying, H. Li, J. Yu, K. M. Ng, F. F. Poon, S. C. C. Wong, A. T.C. Chan, J. J.Y. Sung, and Q. Tao WNT5A Exhibits Tumor-Suppressive Activity through Antagonizing the Wnt/ -Catenin Signaling, and Is Frequently Methylated in Colorectal Cancer Clin. Cancer Res., January 1, 2008; 14(1): 55 - 61. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Boucherat, M.-L. Franco-Montoya, C. Thibault, R. Incitti, B. Chailley-Heu, C. Delacourt, and J. R. Bourbon Gene expression profiling in lung fibroblasts reveals new players in alveolarization Physiol Genomics, December 19, 2007; 32(1): 128 - 141. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Chen, Y. Hu, K. Lu, J. G. Flannery, and J.-x. Ma Very Low Density Lipoprotein Receptor, a Negative Regulator of the wnt Signaling Pathway and Choroidal Neovascularization J. Biol. Chem., November 23, 2007; 282(47): 34420 - 34428. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yamamoto, S. K. Yoo, M. Nishita, A. Kikuchi, and Y. Minami Wnt5a modulates glycogen synthase kinase 3 to induce phosphorylation of receptor tyrosine kinase Ror2. Genes Cells, November 1, 2007; 12(11): 1215 - 1223. [Abstract] [Full Text] [PDF]
|
|
