Fibronectin promotes cell cycle entry in smooth muscle cells in primary culture.
Smooth muscle cell proliferation after arterial injury is regulated by growth factors and components of the extracellular matrix. We have previously demonstrated that fibronectin promotes a phenotypic modulation of freshly isolated rat smooth muscle cells from a contractile to a synthetic phenotype in primary culture and supports the ability of the cells to respond to growth factors. Here, we analyzed if fibronectin promotes cell cycle entry in freshly isolated rat aortic smooth muscle cells during primary culture. Cell cycle analysis showed that cells seeded on fibronectin remained in the G(0)/G(1) phase of the cell cycle during the first 6 days of culture. During this period, there was an increased expression of cyclin D1 and p27(KIP1) in the absence of exogenous growth factors. Addition of serum was followed by enhanced cyclin D1 expression, decreased p27(KIP1) levels, hyperphosphorylation of Rb protein, induction of cyclin A and cyclin D3 expression, and cell cycle progression into S phase. The results indicate that fibronectin initiates cell cycle entry in freshly isolated smooth muscle cells by promoting the induction of cyclin D1 and thereby facilitates further cell cycle progression together with growth factors.
Roy
Joy
J
Department of Surgical Sciences, Karolinska Hospital, Stockholm, Sweden. joy.roy@kirurgi.ki.se
Tran
Phan Kiet
PK
Religa
Piotr
P
Kazi
Monsur
M
Henderson
Bimma
B
Lundmark
Karin
K
Hedin
Ulf
U
D000818:Animals; D001011:Aorta / Q000166:cytology; D002339:Carotid Arteries / Q000378:metabolism; D020212:Carotid Artery Injuries / Q000378:metabolism; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000096:biosynthesis; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000096:biosynthesis; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005353:Fibronectins / Q000378:metabolism*; D016193:G1 Phase; D019833:Genistein / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016192:Resting Phase, Cell Cycle; D016160:Retinoblastoma Protein / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis
C493962:Cdkn1b protein, rat; D018797:Cell Cycle Proteins; D004791:Enzyme Inhibitors; D005353:Fibronectins; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D019833:Genistein