title: Fibronectin stimulates transcription of the platelet-derived growth factor beta-receptor in cultured rat aortic smooth muscle cells.
abstract: Fibronectin seems to play an important role in promoting the characteristic changes of vascular smooth muscle cells in diabetes mellitus including overexpression of the platelet-derived growth factor beta-receptor. To determine the regulatory mechanism of the beta-receptor by fibronectin, we have analyzed the effect of fibronectin on the expression of the beta-receptor in cultured rat aortic smooth muscle cells using the beta-receptor promoter/luciferase expression vector system. Fibronectin was found to stimulate the expression of the beta-receptor at the transcriptional level. Both a MEK1 inhibitor PD98059 and a tyrosine kinase inhibitor herbimycin A significantly inhibited the fibronectin-stimulated receptor transcription. Herbimycin A also completely inhibited the fibronectin-stimulated increase in tyrosine phosphorylation of focal adhesion kinase. These data suggest the involvement of the integrin-mediated mitogen-activated protein kinase pathway downstream of fibronectin stimulation in the activation process of the beta-receptor promoter.
authors.affiliation: Second Department of Internal Medicine, School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, Chuou-ku, 260-0856, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Tamura
authors.forename: K
authors.initials: K
authors.lastname: Yokote
authors.forename: M
authors.initials: M
authors.lastname: Takemoto
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: A
authors.initials: A
authors.lastname: Ishisaki
authors.forename: K
authors.initials: K
authors.lastname: Funa
authors.forename: Y
authors.initials: Y
authors.lastname: Saito
authors.forename: S
authors.initials: S
authors.lastname: Mori
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D016227:Benzoquinones; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005353:Fibronectins / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D017930:Genes, Reporter; D016023:Integrins / Q000378:metabolism; D047029:Lactams, Macrocyclic; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011401:Promoter Regions, Genetic; D047428:Protein Kinase Inhibitors; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor / Q000096:biosynthesis* / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D016227:Benzoquinones; D005353:Fibronectins; D005419:Flavonoids; D016023:Integrins; D047029:Lactams, Macrocyclic; D047428:Protein Kinase Inhibitors; D011809:Quinones; D011993:Recombinant Fusion Proteins; D017828:Rifabutin; C020754:herbimycin; D008156:Luciferases; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor; D017871:Calcium-Calmodulin-Dependent Protein Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one