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First published online 12 September 2006
doi: 10.1242/jcs.03178

Journal of Cell Science 119, 4127-4137 (2006)
Published by The Company of Biologists 2006
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Research Article

Silencing profilin-1 inhibits endothelial cell proliferation, migration and cord morphogenesis

Zhijie Ding1, Anja Lambrechts2, Mayur Parepally3 and Partha Roy1,4,*

1 Department of Bioengineering, University of Pittsburgh, 749 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15261, USA
2 Department of Biochemistry, Ghent University, Albert Baertsoenkaai 3, 9000 Ghent, Belgium
3 Department of Biological Sciences, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213, USA
4 Department of Pathology, University of Pittsburgh, School of Medicine, S-417 BST, 200 Lothrup Street, Pittsburgh, PA 15261, USA

* Author for correspondence (e-mail: proy{at}engr.pitt.edu)

Accepted 20 July 2006

Expression of several actin-binding proteins including profilin-1 is up-regulated during capillary morphogenesis of endothelial cells, the biological significance of which remains unknown. Specifically, we hypothesized that profilin-1 is important for endothelial migration and proliferation. In this study, we suppressed profilin-1 expression in human umbilical vein endothelial cells by RNA-interference. Gene silencing of profilin-1 led to significant reduction in the formation of actin filaments and focal adhesions. Loss of profilin-1 expression was also associated with reduced dynamics of cell-cell adhesion. Data from both wound-healing experiments and time-lapse imaging of individual cells showed inhibition of cell migration when profilin-1 expression was suppressed. Cells lacking profilin-1 exhibited defects in membrane protrusion, both in terms of its magnitude and directional persistence. Furthermore, loss of profilin-1 expression inhibited cell growth without compromising cell survival, at least in the short-term, thus suggesting that profilin-1 also plays an important role in endothelial proliferation as hypothesized. Finally, silencing profilin-1 expression suppressed matrigel-induced early cord morphogenesis of endothelial cells. Taken together, our data suggest that profilin-1 may play important role in biological events that involve endothelial proliferation, migration and morphogenesis.

Key words: Profilin-1, Endothelial cells, Morphogenesis, Migration, Proliferation, Adhesion




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