Fibronectin stimulates transcription of the platelet-derived growth factor beta-receptor in cultured rat aortic smooth muscle cells.
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.
Tamura
K
K
Second Department of Internal Medicine, School of Medicine, Chiba University, 1-8-1 Inohana, Chiba, Chuou-ku, 260-0856, Japan.
Yokote
K
K
Takemoto
M
M
Matsumoto
T
T
Ishisaki
A
A
Funa
K
K
Saito
Y
Y
Mori
S
S
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
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