Silencing profilin-1 inhibits endothelial cell proliferation, migration and cord morphogenesis.
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.
Ding
Zhijie
Z
Department of Bioengineering, University of Pittsburgh, 749 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15261, USA.
Lambrechts
Anja
A
Parepally
Mayur
M
Roy
Partha
P
D000199:Actins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D004622:Embryo, Mammalian / Q000166:cytology; D042783:Endothelial Cells / Q000502:physiology*; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D009024:Morphogenesis / Q000502:physiology*; D051304:Profilins / Q000378:metabolism* / Q000502:physiology*; D034622:RNA Interference / Q000502:physiology; D014470:Umbilical Cord / Q000196:embryology*
D000199:Actins; C495738:PFN1 protein, human; D051304:Profilins