Fibrillar collagen inhibits arterial smooth muscle proliferation through regulation of Cdk2 inhibitors

Arterial smooth muscle cells (SMCs) are arrested in the G1 phase of the cell cycle on polymerized type I collagen fibrils, while monomer collagen supports SMC proliferation. Cyclin E-associated kinase and cyclin-dependent kinase 2 (cdk2) phosphorylation are inhibited on polymerized collagen, and levels of the cdk2 inhibitors p27(Kip1) p21(Cip1/Waf1) increased compared with SMCs on monomer collagen. p27(Kip1) associates with the cyclin E-cdk2-p21(Cip1/Waf1) complex in SMCs on polymerized collagen. Monovalent blocking antibodies to alpha 2 integrins, integrins that mediate adhesion to both forms of collagen, mimic these effects on monomer collagen. Furthermore, polymerized collagen rapidly suppresses p70 S6 kinase, a possible regulator of p27(Kip1). Thus, fibrillar collagen specifically regulates early integrin signaling that may lead to up-regulation of cdk2 inhibitors and inhibition of SMC proliferation.