Syndecan-4 regulates the bFGF-induced chemotactic migration of endothelial cells.

Chemotactic migration of endothelial cells (ECs) guided by extracellular attractants is essential for blood vessel formation. Synd4 is a ubiquitous heparin sulfate proteoglycan receptor on the cell surface that has been identified to promote angiogenesis during tissue repair. Here, the role synd4 played in chemotactic migration of ECs was investigated in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were transfected with Lenti-synd4-RNAi or Lenti-null. Cell migration was observed in a 2D-chemotaxis slide with a stable gradient of basic fibroblast growth factor (bFGF) for 18 h using time-lapse microscopy. Synd4 knockdown HUVECs showed reduced mobility compared with the control. In animal studies, Matrigel premixed with bFGF was used to induce the migration of ECs. The cells migrated less distance from the skin in the Matrigel plugs of synd4 null mice compared with the control mice. Then recombinant adenoviruses containing the synd4 gene (Ad-synd4) or null (Ad-null) were constructed to enhance the synd4 expression of migratory cells in Matrigel plugs of wild-type mice. Migratory cells with synd4 overexpression did not invade further in the Matrigel plugs of wild-type mice, but showed a high ability to proliferate.