Vitronectin regulates smooth muscle contractility via alphav and beta1 integrin.
Previous work from this laboratory has established a method for maintaining physiological contractility of dissociated avian smooth muscle in a defined medium at low density. The present report emphasizes the dramatic potency of serum to alter smooth muscle phenotype and induce a loss of contractility. Vitronectin, a molecule purified from plasma, mimicked these effects of serum via an integrin that is RGD-sensitive. Studies utilizing blocking antibodies against vitronectin demonstrated that the presence of this specific adhesion molecule was necessary for the serum-induced loss of contractility. Based on the actions of function-blocking antibodies and RGD-containing peptides, the integrin alphavbeta1 appears to be the primary receptor involved in vitronectin's ability to induce phenotypic transformation in amniotic smooth muscle. The influence of vitronectin on smooth muscle contractility is particularly relevant, because this molecule is abundant in whole blood and plasma (approx. 400 microg/ml). The results suggest that smooth muscle needs to be continually protected from normal blood constituents in vivo. The implications of these results for smooth muscle-related diseases like atherosclerosis, restenosis and Kaposi's sarcoma are discussed.
Dahm
L M
LM
Division of Neurosciences, Beckman Research Institute of the City of Hope, Duarte, CA 91010, USA.
Bowers
C W
CW
D000650:Amnion; D000818:Animals; D015703:Antigens, CD / Q000187:drug effects* / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D005347:Fibroblasts / Q000166:cytology; D039564:Integrin alphaV; D019012:Integrin beta1 / Q000187:drug effects* / Q000502:physiology; D017136:Ion Transport; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000187:drug effects*; D009842:Oligopeptides / Q000502:physiology; D010641:Phenotype; D019030:Receptors, Vitronectin / Q000187:drug effects / Q000502:physiology*; D019096:Vitronectin / Q000097:blood / Q000494:pharmacology* / Q000502:physiology
D015703:Antigens, CD; D039564:Integrin alphaV; D019012:Integrin beta1; D009842:Oligopeptides; D019030:Receptors, Vitronectin; D019096:Vitronectin; C047981:arginyl-glycyl-aspartic acid; D002118:Calcium