Type I collagen promotes modulation of cultured rabbit arterial smooth muscle cells from a contractile to a synthetic phenotype.
The phenotypic transition of smooth muscle cells (SMC) from a contractile to a synthetic state appears to be an early event in the pathogenesis of atherosclerosis. We examined the effects of extracellular matrix components on the phenotypic modulation of rabbit arterial SMC in primary culture by flow cytometry. The results demonstrate that freshly isolated SMC attached, spread, and started to proliferate on type I collagen as well as on fibronectin. Moreover, type I collagen was as efficient as fibronectin in promoting the transition of the cells into the synthetic phenotype without exogenous mitogens. However, unlike on fibronectin, the synthetic peptide GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro) and the peptide KDGEA (Lys-Asp-Gly-Glu-Ala), which contains the recognition sequence for alpha 2 beta 1 integrin in type I collagen, interfered little with the attachment, spreading, and phenotypic modulation of the cells on type I collagen. On the other hand, the phenotypic modulation of the cells was counteracted by the anti-beta 1 integrin antibody. These findings indicate that type I collagen promotes the phenotypic transition of the rabbit arterial SMC by interacting with a cell surface receptor (beta 1 integrin family) for a cell-binding sequence without RGD and DGEA. In contrast, elastin, a major constituent of the media, suppressed the cell attachment and spreading and maintained the cells in the contractile phenotype as laminin. These results suggest diverse roles of type I collagen and elastin as well as of fibronectin and laminin in the control of the differentiated properties of arterial SMC.
Yamamoto
M
M
Department of Regulation Biology, Faculty of Science, Saitama University, Urawa, Japan.
Yamamoto
K
K
Noumura
T
T
D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen / Q000494:pharmacology*; D005434:Flow Cytometry; D007150:Immunohistochemistry; D008297:Male; D008858:Microscopy, Phase-Contrast; D008969:Molecular Sequence Data; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology; D010641:Phenotype; D011817:Rabbits; D013997:Time Factors
D010455:Peptides; D003094:Collagen