Modulation of α7-integrin-mediated adhesion and expression by platelet-derived growth factor in vascular smooth muscle cells

Jun Tzu Chao, Luis A. Martinez-Lemus, Stephen J. Kaufman, Gerald A. Meininger, Kenneth S. Ramos, Emily Wilson

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

We showed previously that the expression of α7-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 α7-integrin expression and VSMC adhesion and migration. Expression of the α7-integrin gene was determined by real-time RT-PCR, whereas protein levels were determined by fluorescence-activated cell sorting analysis. PDGF increased α7 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 α7- 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- α7-integrin function-blocking antibody. However, PDGF did not alter migration on laminin, and there was no effect of the anti- α7-integrin function-blocking antibody on basal or PDGF-stimulated migration. Immuno-fluorescence imaging revealed an increase in α7-integrin distribution along the stress fibers. Together, these observations indicate that PDGF enhances α7-integrin expression in VSMC and promotes α7-integrin-mediated adhesion to laminin.

Original languageEnglish (US)
Pages (from-to)C972-C980
JournalAmerican Journal of Physiology - Cell Physiology
Volume290
Issue number4
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

Keywords

  • Laminin
  • Mitogen-activated protein kinase
  • Vascular injury

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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