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


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.
Peterson
Timothy E
TE
Mayo Clinic and Foundation, Division of Cardiovascular Diseases, Rochester, MN 55905, USA.
Guicciardi
Maria E
ME
Gulati
Rajiv
R
Kleppe
Laurel S
LS
Mueske
Cheryl S
CS
Mookadam
Martina
M
Sowa
Grzegorz
G
Gores
Gregory J
GJ
Sessa
William C
WC
Simari
Robert D
RD
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051242:Caveolin 1; D022461:Caveolins / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D015536:Down-Regulation / Q000187:drug effects; D005263:Femoral Artery / Q000473:pathology / Q000601:surgery; D006801:Humans; D007083:Iliac Artery / Q000737:chemistry / Q000473:pathology; D007150:Immunohistochemistry / Q000379:methods; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology / Q000502:physiology*; D011817:Rabbits; D015398:Signal Transduction / Q000502:physiology*
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D010982:Platelet-Derived Growth Factor