Modulation of alpha7-integrin-mediated adhesion and expression by platelet-derived growth factor in vascular smooth muscle cells.
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.
Chao
Jun-Tzu
JT
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.
Martinez-Lemus
Luis A
LA
Kaufman
Stephen J
SJ
Meininger
Gerald A
GA
Ramos
Kenneth S
KS
Wilson
Emily
E
D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002448:Cell Adhesion / Q000502:physiology*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000378:metabolism; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D007797:Laminin / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism
D015703:Antigens, CD; D004791:Enzyme Inhibitors; D039001:Integrin alpha Chains; D016023:Integrins; D007797:Laminin; D010982:Platelet-Derived Growth Factor; D021122:Protein Subunits; D016212:Transforming Growth Factor beta; C085725:integrin alpha7; D005346:Fibroblast Growth Factors; D004815:Epidermal Growth Factor; D020928:Mitogen-Activated Protein Kinases; C082908:integrin alpha7beta1