Gp38k, a protein synthesized by vascular smooth muscle cells, stimulates directional migration of human umbilical vein endothelial cells.

Gp38k is a 383-amino-acid secreted glycoprotein expressed by cultured vascular smooth muscle cells during the time of transition from a proliferating monolayer culture to a nonproliferating multilayered (differentiated) culture. Expression continues as the cell culture forms multicellular nodules. Because this transition period involves active cell migration, we evaluated the effects of exogenously added gp38k on vascular endothelial cell (HUVEC) migration and chemotaxis. Here we demonstrate that gp38k acts as a chemoattractant for HUVECs and stimulates cell migration in Boyden chambers at a level comparable to that achieved with the known endothelial cell chemoattractant bFGF. The migration effect is neutralized by the presence of a polyclonal anti-gp38k antibody. Because gp38k expression is also correlated with changes in culture morphology, we also assessed its ability to act as an agonist of HUVEC morphology using cultures growing on Matrigel. We report that gp38k stimulates endothelial cell tubulogenesis in this assay system. These results provide the first evidence that gp38k may function in angiogenesis by stimulating the migration and reorganization of vascular endothelial cells.