Caveolin-1 can regulate vascular smooth muscle cell fate by switching platelet-derived growth factor signaling from a proliferative to an apoptotic pathway

被引:77
作者
Peterson, TE
Guicciardi, ME
Gulati, R
Kleppe, LS
Mueske, CS
Mookadam, M
Sowa, G
Gores, GJ
Sessa, WC
Simari, RD
机构
[1] Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Program Mol Med, Rochester, MN 55905 USA
[2] Mayo Clin & Mayo Fdn, Div Cardiovasc Dis, Dept Biochem & Mol Biol, Rochester, MN 55905 USA
[3] Mayo Clin & Mayo Fdn, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA
[4] Yale Univ, Sch Med, Boyer Ctr Mol Med, Dept Pharmacol, New Haven, CT USA
关键词
caveolae smooth muscle; proliferation; platelet-derived growth factor; apoptosis;
D O I
10.1161/01.ATV.0000081743.35125.05
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:1521 / 1527
页数:7
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