title: Inhibition of vascular smooth muscle cell growth by inhibition of fibronectin matrix assembly.
abstract: The regulation of vascular smooth muscle cell (VSMC) proliferation by the fibronectin matrix was tested by treating human umbilical artery smooth muscle cells (HUASMCs) with a recombinant fragment of fibronectin (protein III1-C) that has previously been shown to modulate fibronectin matrix assembly. III1-C inhibited HUASMC proliferation by 75% to 90%. The inhibition of growth was time dependent; III1-C had no effect on DNA synthesis after 0 to 5 hours of treatment but did have an effect at 24 hours and beyond. III1-C did not stimulate apoptosis in these cells, indicating that the inhibition of proliferation was not due to an induction of programmed cell death. The effects of III1-C on cell growth were only specific for normal diploid smooth muscle cells. III1-C had no effect on the proliferation of IMR-90 fibroblasts, endothelial cells, NIH 3T3 cells, or the rat aortic smooth muscle cell line A7r5. However, III1-C did inhibit proliferation by primary rat aortic smooth muscle cells. An analysis of HUASMC fibronectin receptor (integrin alpha5beta1) distribution revealed that III1-C did not inhibit alpha5beta1 localization to focal contacts. Moreover, III1-C had no effect on the relative expression levels of seven different integrin subunits on HUASMCs. However, III1-C did inhibit fibronectin matrix assembly by rat aortic smooth muscle cells, HUASMCs, A7r5 cells, IMR-90 cells, and endothelial cells. An analysis of fibronectin synthesis indicated that the inhibition of fibronectin matrix assembly by III1-C was not due solely to a decrease in fibronectin synthesis. Finally, treatment of HUASMCs with anti-fibronectin monoclonal antibody L8 (which is known to inhibit fibronectin matrix assembly) also decreased the rate of HUASMC DNA synthesis. These results demonstrate that III1-C inhibits VSMC proliferation and suggest that this effect may be mediated by the inhibition of fibronectin matrix assembly.
authors.affiliation: Department of Pathology, University of Chicago, Ill 60637, USA.
authors.forename: K O
authors.initials: KO
authors.lastname: Mercurius
authors.forename: A O
authors.initials: AO
authors.lastname: Morla
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D016466:CHO Cells / Q000737:chemistry / Q000166:cytology; D002455:Cell Division / Q000187:drug effects; D003094:Collagen; D006224:Cricetinae; D004247:DNA / Q000096:biosynthesis; D004338:Drug Combinations; D005109:Extracellular Matrix / Q000737:chemistry / Q000502:physiology*; D005353:Fibronectins / Q000494:pharmacology*; D006801:Humans; D007797:Laminin / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology* / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D011509:Proteoglycans; D017469:Receptors, Fibronectin / Q000032:analysis; D014469:Umbilical Arteries / Q000166:cytology; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D001672:Biocompatible Materials; D004338:Drug Combinations; D005353:Fibronectins; D007797:Laminin; D010446:Peptide Fragments; D011509:Proteoglycans; D017469:Receptors, Fibronectin; C059485:matrigel; D003094:Collagen; D004247:DNA