Inhibition of smooth muscle cell migration by the p21 cyclin-dependent kinase inhibitor (Cip1).
In vascular smooth muscle cells (SMCs), proliferation and migration contribute to lesion formation after arterial injury. In the cell cycle, several cyclin-dependent kinases (cdks) inhibitors are implicated in the regulating of cyclin-cdk activity such as p21Cip1, p16Ink4 and p27Kip1. Although Cip1 inhibits SMC proliferation, its effects on SMC migration are unknown. To test the hypothesis that Cip1 inhibits SMCs migration and proliferation, we transfected the Cip1 gene into a strain of rabbit aortic SMCs (SM3 cells). Both the spreading and the attachment of Cip1-transfected SM3 cells to extracellular matrices (ECMs) were inhibited compared to that of vector-transfected cells. In the modified Boyden's chamber assay the effect of fibronectin on the migratory activity of Cip1-transfected SM3 cells was significantly less than that of vector transfected cells in response to PDGF-BB. These data suggested that Cip1 inhibited both the migration and proliferation of SMC.
Fukui
R
R
First Department of Internal Medicine, Osaka Medical College, Takatsuki-city, Japan.
Shibata
N
N
Kohbayashi
E
E
Amakawa
M
M
Furutama
D
D
Hoshiga
M
M
Negoro
N
N
Nakakouji
T
T
Ii
M
M
Ishihara
T
T
Ohsawa
N
N
D000199:Actins / Q000032:analysis; D000818:Animals; D001011:Aorta; D002448:Cell Adhesion; D002455:Cell Division; D002465:Cell Movement; D002478:Cells, Cultured; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000502:physiology*; D003599:Cytoskeleton / Q000737:chemistry; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011817:Rabbits; D017469:Receptors, Fibronectin / Q000032:analysis; D011993:Recombinant Fusion Proteins / Q000502:physiology; D015398:Signal Transduction; D014162:Transfection; D016596:Vinculin / Q000032:analysis
D000199:Actins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017469:Receptors, Fibronectin; D011993:Recombinant Fusion Proteins; D016596:Vinculin