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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)

Nyckelord

Animals

Aorta

cytology

drug effects

Benzoquinones

Calcium-Calmodulin-Dependent Protein Kinases

metabolism

Dose-Response Relationship

Drug

Fibronectins

pharmacology

Flavonoids

pharmacology

Genes

Reporter

Integrins

metabolism

Lactams

Macrocyclic

Luciferases

biosynthesis

genetics

Muscle

Smooth

Vascular

drug effects

Promoter Regions

Genetic

Protein Kinase Inhibitors

Quinones

pharmacology

Rats

Receptor

Platelet-Derived Growth Factor beta

Receptors

Platelet-Derived Growth Factor

biosynthesis

genetics

Recombinant Fusion Proteins

biosynthesis

Rifabutin

analogs & derivatives

Signal Transduction

Transcription

Genetic

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)