Del1 mediates VSMC adhesion, migration, and proliferation through interaction with integrin alpha(v)beta(3).
Del1 is a matrix protein transiently expressed by embryonic endothelial cells. It was recently demonstrated that vascular endothelial cells adhere and interact with Del1 through alpha(v)beta(3)- integrins, providing an autocrine angiogenic signaling pathway in this cell type. To determine whether Del1 might signal to other cell types in the vessel wall in a paracrine fashion, studies were conducted with vascular smooth muscle cells (VSMC). Del1 promoted adhesion and migration of VSMC in a dose-dependent fashion. These functions were mediated through alpha(v)beta(3)-integrins, as the vitronectin receptor inhibitory peptide containing penacillamine (PCN) arginine-glycine-aspartic acid (PCN-RGD) and an antibody specific for the alpha(v)beta(3)-integrin specifically blocked both adhesion and migration. Adhesion of VSMC to Del1 was associated with organization of actin filaments and formation of focal contacts enriched in vinculin and alpha(v)beta(3). Furthermore, Del1 supported VSMC proliferation at least in part by inhibiting these cells from undergoing apoptosis. These data, in conjunction with evidence that Del1 expression is reactivated in vascular injury, suggest that Del1 may have a paracrine role in vessel wall development and remodeling.
Rezaee
Mehrdad
M
Donald W. Reynolds Cardiovascular Clinical Research Center, Stanford University School of Medicine, Stanford, California 94305, USA.
Penta
Kalyani
K
Quertermous
Thomas
T
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D016367:Baculoviridae / Q000235:genetics; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology*; D015815:Cell Adhesion Molecules; D002455:Cell Division / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002633:Chemotaxis; D004622:Embryo, Mammalian; D004625:Embryo, Nonmammalian; D004730:Endothelium, Vascular / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D020287:In Situ Nick-End Labeling; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D018919:Neovascularization, Physiologic; D009842:Oligopeptides / Q000494:pharmacology; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D018411:Spodoptera / Q000378:metabolism
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C110183:EDIL3 protein, human; D009842:Oligopeptides; D019030:Receptors, Vitronectin; D011994:Recombinant Proteins; C047981:arginyl-glycyl-aspartic acid