Abstract
Background - Caveolin-1 is a regulator of signaling events originating from plasma membrane microdomains termed caveolae. This study was performed to determine the regulatory role of caveolin-1 on the proliferative events induced by platelet-derived growth factor (PDGF) in vascular smooth muscle cells (VSMCs). Methods and Results - Treatment of VSMCs with PDGF for 24 hours resulted in a loss of caveolin-1 protein expression and plasma membrane-associated caveolae, despite a 3-fold increase in caveolin-1 mRNA. Pretreatment of VSMCs with chloroquine, an inhibitor of lysosomal function, inhibited the PDGF-induced loss of caveolin-1. These studies demonstrated that caveolin-1 was a target of PDGF signaling events. Adenoviral overexpression of caveolin-1 was associated with a switch in PDGF-induced signaling events from a proliferative response to an apoptotic response. This overexpression inhibited PDGF-induced expression of cyclin D1 in the presence of unaffected mitogen-activated protein kinase activation. Conclusions - Taken together, these studies suggest that caveolin-1 is an inhibitor of PDGF proliferative responses and might be capable of transforming PDGF-induced proliferative signals into death signals.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1521-1527 |
| Number of pages | 7 |
| Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
| Volume | 23 |
| Issue number | 9 |
| DOIs | |
| State | Published - Sep 1 2003 |
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Keywords
- Apoptosis
- Caveolae
- Platelet-derived growth factor
- Proliferation
- Smooth muscle
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
Cite this
Caveolin-1 can regulate vascular smooth muscle cell fate by switching platelet-derived growth factor signaling from a proliferative to an apoptotic pathway. / Peterson, Timothy E.; Guicciardi, Maria E.; Gulati, Rajiv; Kleppe, Laurel S.; Mueske, Cheryl S.; Mookadam, Martina; Sowa, Grzegorz; Gores, Gregory James; Sessa, William C.; Simari, Robert D.
In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 23, No. 9, 01.09.2003, p. 1521-1527.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Caveolin-1 can regulate vascular smooth muscle cell fate by switching platelet-derived growth factor signaling from a proliferative to an apoptotic pathway
AU - Peterson, Timothy E.
AU - Guicciardi, Maria E.
AU - Gulati, Rajiv
AU - Kleppe, Laurel S.
AU - Mueske, Cheryl S.
AU - Mookadam, Martina
AU - Sowa, Grzegorz
AU - Gores, Gregory James
AU - Sessa, William C.
AU - Simari, Robert D.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - Background - Caveolin-1 is a regulator of signaling events originating from plasma membrane microdomains termed caveolae. This study was performed to determine the regulatory role of caveolin-1 on the proliferative events induced by platelet-derived growth factor (PDGF) in vascular smooth muscle cells (VSMCs). Methods and Results - Treatment of VSMCs with PDGF for 24 hours resulted in a loss of caveolin-1 protein expression and plasma membrane-associated caveolae, despite a 3-fold increase in caveolin-1 mRNA. Pretreatment of VSMCs with chloroquine, an inhibitor of lysosomal function, inhibited the PDGF-induced loss of caveolin-1. These studies demonstrated that caveolin-1 was a target of PDGF signaling events. Adenoviral overexpression of caveolin-1 was associated with a switch in PDGF-induced signaling events from a proliferative response to an apoptotic response. This overexpression inhibited PDGF-induced expression of cyclin D1 in the presence of unaffected mitogen-activated protein kinase activation. Conclusions - Taken together, these studies suggest that caveolin-1 is an inhibitor of PDGF proliferative responses and might be capable of transforming PDGF-induced proliferative signals into death signals.
AB - Background - Caveolin-1 is a regulator of signaling events originating from plasma membrane microdomains termed caveolae. This study was performed to determine the regulatory role of caveolin-1 on the proliferative events induced by platelet-derived growth factor (PDGF) in vascular smooth muscle cells (VSMCs). Methods and Results - Treatment of VSMCs with PDGF for 24 hours resulted in a loss of caveolin-1 protein expression and plasma membrane-associated caveolae, despite a 3-fold increase in caveolin-1 mRNA. Pretreatment of VSMCs with chloroquine, an inhibitor of lysosomal function, inhibited the PDGF-induced loss of caveolin-1. These studies demonstrated that caveolin-1 was a target of PDGF signaling events. Adenoviral overexpression of caveolin-1 was associated with a switch in PDGF-induced signaling events from a proliferative response to an apoptotic response. This overexpression inhibited PDGF-induced expression of cyclin D1 in the presence of unaffected mitogen-activated protein kinase activation. Conclusions - Taken together, these studies suggest that caveolin-1 is an inhibitor of PDGF proliferative responses and might be capable of transforming PDGF-induced proliferative signals into death signals.
KW - Apoptosis
KW - Caveolae
KW - Platelet-derived growth factor
KW - Proliferation
KW - Smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=10744223342&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=10744223342&partnerID=8YFLogxK
U2 - 10.1161/01.ATV.0000081743.35125.05
DO - 10.1161/01.ATV.0000081743.35125.05
M3 - Article
VL - 23
SP - 1521
EP - 1527
JO - Arteriosclerosis, Thrombosis, and Vascular Biology
JF - Arteriosclerosis, Thrombosis, and Vascular Biology
SN - 1079-5642
IS - 9
ER -