Wnt-1 signaling inhibits human umbilical vein endothelial cell proliferation and alters cell morphology.
Cell to cell interaction is one of the key processes effecting angiogenesis and endothelial cell function. There are many factors which can mediate this interaction including Wnt-signaling-related molecules. Wnt signaling is involved in many developmental processes and cellular functions. There is increasing evidence suggesting that Wnt signaling has a role in regulating endothelial cell growth although the precise mechanism is unclear. In this study, we established a coculture system to examine how Wnt-1 signaling regulates human umbilical vein endothelial cell (HUVEC) growth and behavior. We found that Wnt-1 signals inhibited BrdU incorporation in HUVECs and the number of labeled cells also decreased in proportion to the number of Wnt-1-expressing cells present (P < 0.05). Moreover, HUVECs cocultured with Wnt-1-expressing C57MG cells clumped together rather than remaining scattered throughout the culture. These effects were dependent on cell contact. Treatment of HUVEC with LiCl, which inhibits the activity of GSK-3beta and mimicked Wnt-1 signaling, also inhibited the BrdU incorporation in endothelial cells. Our results suggest that Wnt signaling has a role in endothelial cell growth control and this is mediated through cell-cell contact. They also suggest that Wnt signaling might participate in angiogenesis by regulating endothelial cell growth and function.
Cheng
Ching-wen
CW
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Smith
Stephen K
SK
Charnock-Jones
D Stephen
DS
D002448:Cell Adhesion; D002450:Cell Communication; D002455:Cell Division; D048429:Cell Size; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology*; D006801:Humans; D018919:Neovascularization, Physiologic; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014471:Umbilical Veins / Q000166:cytology*; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins
D011518:Proto-Oncogene Proteins; C495247:WNT1 protein, human; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins