Biochemical and Biophysical Research Communications
Type I collagen synergistically enhances PDGF-induced smooth muscle cell proliferation through pp60src-dependent crosstalk between the α2β1 integrin and PDGFβ receptor
Section snippets
Materials and methods
General materials. Human recombinant PDGF-BB was purchased from Upstate Biotechnologies (Lake Placid, NY). Collagen type I from calf skin, collagen type IV (CNIV), laminin, smooth muscle specific actin immunostaining kit, ethylene glycol-bis(b-aminoethyl ether)-N,N,N′,N′-tetraacetic acid (EGTA), ethylenediaminetetraacetic acid (EDTA), phenylmethylsulfonyl fluoride (PMSF), adenosine 5′-triphosphate (ATP, disodium salt), sodium dodecyl sulfate (SDS), Nonidet-P40, and Triton X-100 were from Sigma
CNI synergistically enhances PDGF-BB-induced smooth muscle cell proliferation
We investigated the potential for laminin (1–50 μg/ml), CNI (1–50 μg/ml) or CNIV (1–50 μg/ml) to induce SMC proliferation. Of the ECM proteins studied, only CNI significantly enhanced tritiated thymidine incorporation. This effect was concentration dependent, first evident at 10 μg/ml (fold increase over control = 1.4 ± 0.1) and increased at 20 μg/ml (fold increase over control = 1.7 ± 0.4). The effect was most pronounced at 50 μg/ml (fold increase over control = 2.1 ± 0.5). We observed no increase in SMC
Discussion
We have characterized a novel synergistic interaction between CNI and PDGF-BB in promoting human vascular SMC proliferation. Our data demonstrate that the signaling pathways activated by PDGF-BB that lead to proliferation of vascular SMC are enhanced by CNI via an interaction that involves the α2β1 integrin. In sum, the α2β1 integrin in an interaction mediated by pp60src produces synergistic enhancement of PDGFRβ tyrosine phosphorylation as well as activation of ERK2 and consequently enhanced
Acknowledgments
This project was supported by the National Institute of Health Grants HL55465 (Kent), HL68673 (Kent), and T32 CA68971 (Hollenbeck) and the Association for Academic Surgery Research Fellowship Award (Hollenbeck).
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