16282198

pubmed:Citation

4

We showed previously that the expression of alpha(7)-integrin in aortic vascular smooth muscle cells (VSMC) is enhanced in a rat model of atherosclerosis. In the present study, we investigated the effects of platelet-derived growth factor (PDGF) on alpha(7)-integrin expression and VSMC adhesion and migration. Expression of the alpha(7)-integrin gene was determined by real-time RT-PCR, whereas protein levels were determined by fluorescence-activated cell sorting analysis. PDGF increased alpha(7) cell surface protein expression (12 and 24 h: 3.3 +/- 0.8- and 3.6 +/- 0.4-fold, P < 0.05 vs. control) and mRNA levels (24 h: 3.1-fold, P < 0.05 vs. control) in a time-dependent manner. Actinomycin D and cycloheximide attenuated PDGF-induced increases in alpha(7)-integrin, indicating the involvement of de novo mRNA and protein synthesis. Treatment with the MAPK inhibitors PD-98059, SP-600125, and SB-203580 attenuated PDGF-induced increases in mRNA. In contrast, PD-98059 and SP-600125, but not SB-203580, attenuated PDGF-induced increases in cell surface protein levels. PDGF-treated VSMC adhered to laminin more efficiently (42 +/- 6% increase, P < 0.01), and this increase was partially inhibited by anti-alpha(7)-integrin function-blocking antibody. However, PDGF did not alter migration on laminin, and there was no effect of the anti-alpha(7)-integrin function-blocking antibody on basal or PDGF-stimulated migration. Immunofluorescence imaging revealed an increase in alpha(7)-integrin distribution along the stress fibers. Together, these observations indicate that PDGF enhances alpha(7)-integrin expression in VSMC and promotes alpha(7)-integrin-mediated adhesion to laminin.

eng

IM

MEDLINE

0363-6143

Print

NLM

C972-80

pubmed-meshheading:16282198-Animals, pubmed-meshheading:16282198-Antigens, CD, pubmed-meshheading:16282198-Cell Adhesion, pubmed-meshheading:16282198-Cells, Cultured, pubmed-meshheading:16282198-Enzyme Inhibitors, pubmed-meshheading:16282198-Epidermal Growth Factor, pubmed-meshheading:16282198-Fibroblast Growth Factors, pubmed-meshheading:16282198-Humans, pubmed-meshheading:16282198-Integrin alpha Chains, pubmed-meshheading:16282198-Integrins, pubmed-meshheading:16282198-Laminin, pubmed-meshheading:16282198-MAP Kinase Signaling System, pubmed-meshheading:16282198-Mitogen-Activated Protein Kinases, pubmed-meshheading:16282198-Muscle, Smooth, Vascular, pubmed-meshheading:16282198-Myocytes, Smooth Muscle, pubmed-meshheading:16282198-Platelet-Derived Growth Factor, pubmed-meshheading:16282198-Protein Subunits, pubmed-meshheading:16282198-Rats, pubmed-meshheading:16282198-Rats, Sprague-Dawley, pubmed-meshheading:16282198-Transcription, Genetic, pubmed-meshheading:16282198-Transforming Growth Factor beta

Modulation of alpha7-integrin-mediated adhesion and expression by platelet-derived growth factor in vascular smooth muscle cells.

Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural