Fibrillar collagen regulation of plasminogen activator inhibitor-1 is involved in altered smooth muscle cell migration.
OBJECTIVE
Vascular smooth muscle cells (SMCs) cultured on polymerized type I collagen fibrils are arrested in the G1 phase of the cell cycle, and their phenotypic markers and pattern of expressed genes are markedly altered. In this study, we examined polymerized collagen regulation of plasminogen activator inhibitor (PAI)-1 and its involvement in SMC migration.


RESULTS
We demonstrate that secretion and cell surface accumulation of PAI-1 are suppressed in SMCs cultured on polymerized collagen compared with SMCs cultured on monomer collagen. SMCs replated on vitronectin after culture on monomer collagen result in PAI-1 accumulation at focal adhesions and colocalization with alpha(v)beta3 integrins. In contrast, polymerized collagen inhibits PAI-1 accumulation at focal adhesions when the SMCs are replated on vitronectin. Furthermore, for SMCs cultured on polymerized collagen, platelet-derived growth factor-stimulated migration on vitronectin is enhanced by PAI-1, with its function counteracted by urinary plasminogen activator. Finally, exogenous addition of PAI-1 appears to partly restore platelet-derived growth factor-stimulated alpha(v)beta3-dependent SMC migration that is specifically suppressed by polymerized collagen.


CONCLUSIONS
Polymerized type I collagen fibrils dynamically regulate PAI-1, which may be involved in altered alpha(v)beta3 integrin-dependent SMC migration.
Tanaka
Shinji
S
Department of Metabolism, Endocrinology, and Molecular Medicine, Osaka City University Graduate School of Medicine, Osaka, Japan.
Koyama
Hidenori
H
Ichii
Takuya
T
Shioi
Atsushi
A
Hosoi
Masayuki
M
Raines
Elaine W
EW
Nishizawa
Yoshiki
Y
D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism; D024022:Fibrillar Collagens / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000378:metabolism / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011108:Polymers / Q000378:metabolism / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D055293:Receptors, Urokinase Plasminogen Activator; D019030:Receptors, Vitronectin / Q000378:metabolism; D014469:Umbilical Arteries / Q000166:cytology; D014568:Urokinase-Type Plasminogen Activator / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D019096:Vitronectin / Q000378:metabolism / Q000494:pharmacology
D024042:Collagen Type I; D024022:Fibrillar Collagens; D008565:Membrane Proteins; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D010982:Platelet-Derived Growth Factor; D011108:Polymers; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D019030:Receptors, Vitronectin; D019096:Vitronectin; D014568:Urokinase-Type Plasminogen Activator