Modulation of alpha7-integrin-mediated adhesion and expression by platelet-derived growth factor in vascular smooth muscle cells |
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Authors: | Chao Jun-Tzu Martinez-Lemus Luis A Kaufman Stephen J Meininger Gerald A Ramos Kenneth S Wilson Emily |
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Affiliation: | Division of Vascular Biology, Cardiovascular Research Institute, The Texas A&M University System Health Science Center, 336 Joe Reynolds Medical Bldg., College Station, 77843, USA. |
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Abstract: | We showed previously that the expression of 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 7-integrin expression and VSMC adhesion and migration. Expression of the 7-integrin gene was determined by real-time RT-PCR, whereas protein levels were determined by fluorescence-activated cell sorting analysis. PDGF increased 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 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-7-integrin function-blocking antibody. However, PDGF did not alter migration on laminin, and there was no effect of the anti-7-integrin function-blocking antibody on basal or PDGF-stimulated migration. Immunofluorescence imaging revealed an increase in 7-integrin distribution along the stress fibers. Together, these observations indicate that PDGF enhances 7-integrin expression in VSMC and promotes 7-integrin-mediated adhesion to laminin. vascular injury; laminin; mitogen-activated protein kinase |
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