The urokinase receptor mediates basic fibroblast growth factor-dependent smooth muscle cell migration through baboon aortic explants.
The urokinase receptor is required for vascular smooth muscle cell migration in vitro, but may not be needed in vivo since smooth muscle cell migration and intimal hyperplasia after arterial injury in mice are not affected by urokinase receptor gene deletion. We have used baboon aortic explants as a bridge between cell culture and in vivo experiments to determine if the urokinase receptor is required for smooth muscle cell proliferation and smooth muscle cell migration in primate vessels. Levels of urokinase receptor in explants increased with time after explantation, while blockade of urokinase receptor with an antibody decreased smooth muscle cell proliferation and smooth muscle cell migration from the explants. A blocking antibody to basic fibroblast growth decreased levels of urokinase and urokinase receptor in explants, and it decreased smooth muscle cell migration and mitogenesis. These results suggest that the factor urokinase receptor plays a positive role in smooth muscle cell migration and proliferation in injured primate arterial tissue, in part mediating the pro-migratory and proliferative effects of basic fibroblast growth factor released by damaged smooth muscle cells.
Kenagy
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Department of Surgery, School of Medicine, University of Washington, Box 356410, AA404, Health Sciences Building, Seattle, WA 98195-6410, USA. rkenagy@u.washington.edu
Vesti
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Clowes
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D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000166:cytology* / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects*; D004306:Dose-Response Relationship, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology* / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000187:drug effects* / Q000502:physiology*; D020778:Matrix Metalloproteinase 2 / Q000187:drug effects; D023421:Models, Animal; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects*; D010215:Papio; D010960:Plasminogen Activators / Q000187:drug effects / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000187:drug effects / Q000502:physiology*
D019138:Antibodies, Blocking; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D016222:Fibroblast Growth Factor 2; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator; D020778:Matrix Metalloproteinase 2