Abstract
Smooth muscle cells (SMCs) are exposed to both platelet-derived growth factor (PDGF) and type I collagen (CNI) at the time of arterial injury. In these studies we explore the individual and combined effects of these agonists on human saphenous vein SMC proliferation. PDGF-BB produced a 5.5-fold increase in SMC DNA synthesis whereas CNI stimulated DNA synthesis to a much lesser extent (1.6-fold increase). Alternatively, we observed an 8.3-fold increase in DNA synthesis when SMCs were co-incubated with CNI and PDGF-BB. Furthermore, stimulation of SMCs with PDGF-BB produced a significant increase in ERK-2 activity whereas CNI alone had no effect. Co-incubation of SMCs with PDGF-BB and CNI resulted in ERK-2 activity that was markedly greater than that produced by PDGF-BB alone. In a similar fashion, PDGF-BB induced phosphorylation of the PDGF receptor {beta} (PDGFR{beta}) and CNI did not, whereas concurrent agonist stimulation produced a synergistic increase in receptor activity. Blocking antibodies to the {alpha}2 and {beta}1 subunits eliminated this synergistic interaction, implicating the {alpha}2{beta}1 integrin as the mediator of this effect. Immunoprecipitation of the {alpha}2{beta}1 integrin in unstimulated SMCs followed by immunoblotting for the PDGFR{beta} as well as Src family members, pp60{sup src}, Fyn, Lyn, and Yes demonstrated coassociation of {alpha}2{beta}1
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Hollenbeck, Scott T;
[1]
Itoh, Hiroyuki;
[1]
Louie, Otway;
[1]
Faries, Peter L;
[1]
Columbia Weill Cornell Division of Vascular Surgery, Columbia College of Physicians and Surgeons (United States)];
Bo, Liu;
[1]
Kent, K Craig
[2]
- Columbia Weill Cornell Division of Vascular Surgery, Weill Medical College of Cornell University (United States)
- Columbia Weill Cornell Division of Vascular Surgery, Weill Medical College of Cornell University (United States) and Columbia Weill Cornell Division of Vascular Surgery, Columbia College of Physicians and Surgeons (United States)
Citation Formats
Hollenbeck, Scott T, Itoh, Hiroyuki, Louie, Otway, Faries, Peter L, Columbia Weill Cornell Division of Vascular Surgery, Columbia College of Physicians and Surgeons (United States)], Bo, Liu, and Kent, K Craig.
Type I collagen synergistically enhances PDGF-induced smooth muscle cell proliferation through pp60{sup src}-dependent crosstalk between the {alpha}2{beta}1 integrin and PDGF{beta} receptor.
United States: N. p.,
2004.
Web.
doi:10.1016/j.bbrc.2004.10.031.
Hollenbeck, Scott T, Itoh, Hiroyuki, Louie, Otway, Faries, Peter L, Columbia Weill Cornell Division of Vascular Surgery, Columbia College of Physicians and Surgeons (United States)], Bo, Liu, & Kent, K Craig.
Type I collagen synergistically enhances PDGF-induced smooth muscle cell proliferation through pp60{sup src}-dependent crosstalk between the {alpha}2{beta}1 integrin and PDGF{beta} receptor.
United States.
https://doi.org/10.1016/j.bbrc.2004.10.031
Hollenbeck, Scott T, Itoh, Hiroyuki, Louie, Otway, Faries, Peter L, Columbia Weill Cornell Division of Vascular Surgery, Columbia College of Physicians and Surgeons (United States)], Bo, Liu, and Kent, K Craig.
2004.
"Type I collagen synergistically enhances PDGF-induced smooth muscle cell proliferation through pp60{sup src}-dependent crosstalk between the {alpha}2{beta}1 integrin and PDGF{beta} receptor."
United States.
https://doi.org/10.1016/j.bbrc.2004.10.031.
@misc{etde_20615223,
title = {Type I collagen synergistically enhances PDGF-induced smooth muscle cell proliferation through pp60{sup src}-dependent crosstalk between the {alpha}2{beta}1 integrin and PDGF{beta} receptor}
author = {Hollenbeck, Scott T, Itoh, Hiroyuki, Louie, Otway, Faries, Peter L, Columbia Weill Cornell Division of Vascular Surgery, Columbia College of Physicians and Surgeons (United States)], Bo, Liu, and Kent, K Craig}
abstractNote = {Smooth muscle cells (SMCs) are exposed to both platelet-derived growth factor (PDGF) and type I collagen (CNI) at the time of arterial injury. In these studies we explore the individual and combined effects of these agonists on human saphenous vein SMC proliferation. PDGF-BB produced a 5.5-fold increase in SMC DNA synthesis whereas CNI stimulated DNA synthesis to a much lesser extent (1.6-fold increase). Alternatively, we observed an 8.3-fold increase in DNA synthesis when SMCs were co-incubated with CNI and PDGF-BB. Furthermore, stimulation of SMCs with PDGF-BB produced a significant increase in ERK-2 activity whereas CNI alone had no effect. Co-incubation of SMCs with PDGF-BB and CNI resulted in ERK-2 activity that was markedly greater than that produced by PDGF-BB alone. In a similar fashion, PDGF-BB induced phosphorylation of the PDGF receptor {beta} (PDGFR{beta}) and CNI did not, whereas concurrent agonist stimulation produced a synergistic increase in receptor activity. Blocking antibodies to the {alpha}2 and {beta}1 subunits eliminated this synergistic interaction, implicating the {alpha}2{beta}1 integrin as the mediator of this effect. Immunoprecipitation of the {alpha}2{beta}1 integrin in unstimulated SMCs followed by immunoblotting for the PDGFR{beta} as well as Src family members, pp60{sup src}, Fyn, Lyn, and Yes demonstrated coassociation of {alpha}2{beta}1 and the PDGFR{beta} as well as pp60{sup src}. Incubation of cells with CNI and/or PDGF-BB did not change the degree of association. Finally, inhibition of Src activity with SU6656 eliminated the synergistic effect of CNI on PDGF-induced PDGFR{beta} phosphorylation suggesting an important role for pp60{sup src} in the observed receptor crosstalk. Together, these data demonstrate that CNI synergistically enhances PDGF-induced SMC proliferation through Src-dependent crosstalk between the {alpha}2{beta}1 integrin and the PDGFR{beta}.}
doi = {10.1016/j.bbrc.2004.10.031}
journal = []
issue = {1}
volume = {325}
journal type = {AC}
place = {United States}
year = {2004}
month = {Dec}
}
title = {Type I collagen synergistically enhances PDGF-induced smooth muscle cell proliferation through pp60{sup src}-dependent crosstalk between the {alpha}2{beta}1 integrin and PDGF{beta} receptor}
author = {Hollenbeck, Scott T, Itoh, Hiroyuki, Louie, Otway, Faries, Peter L, Columbia Weill Cornell Division of Vascular Surgery, Columbia College of Physicians and Surgeons (United States)], Bo, Liu, and Kent, K Craig}
abstractNote = {Smooth muscle cells (SMCs) are exposed to both platelet-derived growth factor (PDGF) and type I collagen (CNI) at the time of arterial injury. In these studies we explore the individual and combined effects of these agonists on human saphenous vein SMC proliferation. PDGF-BB produced a 5.5-fold increase in SMC DNA synthesis whereas CNI stimulated DNA synthesis to a much lesser extent (1.6-fold increase). Alternatively, we observed an 8.3-fold increase in DNA synthesis when SMCs were co-incubated with CNI and PDGF-BB. Furthermore, stimulation of SMCs with PDGF-BB produced a significant increase in ERK-2 activity whereas CNI alone had no effect. Co-incubation of SMCs with PDGF-BB and CNI resulted in ERK-2 activity that was markedly greater than that produced by PDGF-BB alone. In a similar fashion, PDGF-BB induced phosphorylation of the PDGF receptor {beta} (PDGFR{beta}) and CNI did not, whereas concurrent agonist stimulation produced a synergistic increase in receptor activity. Blocking antibodies to the {alpha}2 and {beta}1 subunits eliminated this synergistic interaction, implicating the {alpha}2{beta}1 integrin as the mediator of this effect. Immunoprecipitation of the {alpha}2{beta}1 integrin in unstimulated SMCs followed by immunoblotting for the PDGFR{beta} as well as Src family members, pp60{sup src}, Fyn, Lyn, and Yes demonstrated coassociation of {alpha}2{beta}1 and the PDGFR{beta} as well as pp60{sup src}. Incubation of cells with CNI and/or PDGF-BB did not change the degree of association. Finally, inhibition of Src activity with SU6656 eliminated the synergistic effect of CNI on PDGF-induced PDGFR{beta} phosphorylation suggesting an important role for pp60{sup src} in the observed receptor crosstalk. Together, these data demonstrate that CNI synergistically enhances PDGF-induced SMC proliferation through Src-dependent crosstalk between the {alpha}2{beta}1 integrin and the PDGFR{beta}.}
doi = {10.1016/j.bbrc.2004.10.031}
journal = []
issue = {1}
volume = {325}
journal type = {AC}
place = {United States}
year = {2004}
month = {Dec}
}