© 1997 American Heart Association, Inc.
Articles |
Fibroblast Growth Factor-2 Potentiates Vascular Smooth Muscle Cell Migration to Platelet-Derived Growth Factor
Upregulation of 
2ß1 Integrin and Disassembly of Actin Filaments
From the John P. Robarts Research Institute and London Health Sciences Centre, Departments of Medicine (Cardiology) (J.G.P., C.M.F., M.A.L., L.H.C.), Medical Biophysics (J.G.P., C.G.E., J.F.), Biochemistry (J.G.P.), and Microbiology and Immunology (S.U., T.C., B.M.C.C.), University of Western Ontario, London, Canada.
Correspondence to J. Geoffrey Pickering, London Health Sciences Centre, 339 Windermere Rd, London, Ontario N6A 5A5, Canada. E-mail gpickrng{at}rri.uwo.ca
Abstract Fibroblast growth factor-2 (FGF-2) has been
implicated in vascular smooth muscle cell (SMC) migration, a key
process in vascular disease. We demonstrate here that FGF-2 promotes
SMC motility by altering ß1 integrin–mediated
interactions with the extracellular matrix (ECM). FGF-2 significantly
increased surface expression of 2ß1,
3ß1, and 5ß1
integrins on human SMCs, as assessed by flow cytometry. The greatest
increase was for the collagen-binding 2ß1
integrin. Despite this, FGF-2 did not increase SMC adhesion to type I
collagen but instead promoted SMC elongation and SMC motility. The
latter was evaluated by using a microchemotaxis chamber and by digital
time-lapse video microscopy. Although FGF-2 was not chemotactic for
human SMCs, cells preincubated with FGF-2 displayed a 3.1-fold increase
in migration to the undersurface of porous type I collagen–coated
membranes and a 2.1-fold increase in migration speed on collagen.
Furthermore, chemotaxis to platelet-derived growth factor-BB on
collagen was significantly greater in SMCs exposed to FGF-2.
FGF-2–induced elongation and migration on collagen were inhibited by a
blocking anti-2ß1 antibody; however, SMC
adhesion to collagen was unaffected. SMC migration on fibronectin was
also enhanced by FGF-2, although less prominently: migration through
porous membranes increased 1.8-fold, and migration speed increased
1.3-fold. Also, FGF-2 completely disassembled the smooth muscle
-actin–containing stress fiber network contemporaneously with the
change in integrin expression and cell shape. We conclude that (1)
exogenous FGF-2 promotes SMC migration and potentiates chemotaxis to
PDGF-BB; (2) the promigratory effect of FGF-2 is especially prominent
on type I collagen and is mediated by upregulation of
2ß1 integrin; and (3) FGF-2 disassembles
actin stress fibers, which may promote differential utilization of
2ß1 integrin for motility but not
adhesion. This dynamic SMC-ECM interplay may be an important mechanism
by which FGF-2 facilitates SMC motility in vivo.
Key Words: smooth muscle cell • integrin • collagen • actin • fibroblast growth factor
This article has been cited by other articles:
 |
|
 |
|
  M. J. Frontini, C. O'Neil, C. Sawyez, B. M.C. Chan, M. W. Huff, and J. G. Pickering Lipid Incorporation Inhibits Src-Dependent Assembly of Fibronectin and Type I Collagen by Vascular Smooth Muscle Cells Circ. Res., April 10, 2009; 104(7): 832 - 841. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Schroder, I. Helmcke, K. Palfi, K.-H. Krause, R. Busse, and R. P. Brandes Nox1 Mediates Basic Fibroblast Growth Factor-Induced Migration of Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1736 - 1743. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Filippov, G. C. Koenig, T.-H. Chun, K. B. Hotary, I. Ota, T. H. Bugge, J. D. Roberts, W. P. Fay, H. Birkedal-Hansen, K. Holmbeck, et al. MT1-matrix metalloproteinase directs arterial wall invasion and neointima formation by vascular smooth muscle cells J. Exp. Med., September 6, 2005; 202(5): 663 - 671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. H. O'Neil, M. B. Boffa, M. A. Hancock, J. G. Pickering, and M. L. Koschinsky Stimulation of Vascular Smooth Muscle Cell Proliferation and Migration by Apolipoprotein(a) Is Dependent on Inhibition of Transforming Growth Factor-{beta} Activation and on the Presence of Kringle IV Type 9 J. Biol. Chem., December 31, 2004; 279(53): 55187 - 55195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Fera, C. O'Neil, W. Lee, S. Li, and J. G. Pickering Fibroblast Growth Factor-2 and Remodeled Type I Collagen Control Membrane Protrusion in Human Vascular Smooth Muscle Cells: BIPHASIC ACTIVATION OF Rac1 J. Biol. Chem., August 20, 2004; 279(34): 35573 - 35582. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Li, C. Van Den Diepstraten, S. J. D'Souza, B. M. C. Chan, and J. G. Pickering Vascular Smooth Muscle Cells Orchestrate the Assembly of Type I Collagen via {alpha}2{beta}1 Integrin, RhoA, and Fibronectin Polymerization Am. J. Pathol., September 1, 2003; 163(3): 1045 - 1056. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. P. Moiseeva Adhesion receptors of vascular smooth muscle cells and their functions Cardiovasc Res, December 1, 2001; 52(3): 372 - 386. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Watanabe, M. Kurabayashi, M. Arai, K. Sekiguchi, and R. Nagai Combined effect of retinoic acid and basic FGF on PAI-1 gene expression in vascular smooth muscle cells Cardiovasc Res, July 1, 2001; 51(1): 151 - 159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. Korah, V. Sysounthone, Y. Golowa, and R. Wieder Basic Fibroblast Growth Factor Confers a Less Malignant Phenotype in MDA-MB-231 Human Breast Cancer Cells Cancer Res., February 1, 2000; 60(3): 733 - 740. [Abstract] [Full Text]
|
|
|
|
|
|
J. G. Pickering, L. H. Chow, S. Li, K. A. Rogers, E. F. Rocnik, R. Zhong, and B. M. C. Chan {alpha}5{beta}1 Integrin Expression and Luminal Edge Fibronectin Matrix Assembly by Smooth Muscle Cells after Arterial Injury Am. J. Pathol., February 1, 2000; 156(2): 453 - 465. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Facchiano, F De Marchis, E Turchetti, F Facchiano, M Guglielmi, A Denaro, R Palumbo, M Scoccianti, and M. Capogrossi The chemotactic and mitogenic effects of platelet-derived growth factor-BB on rat aorta smooth muscle cells are inhibited by basic fibroblast growth factor J. Cell Sci., January 8, 2000; 113(16): 2855 - 2863. [Abstract] [PDF]
|
|
|
|
|
|
E Stringa, V Knauper, G Murphy, and J Gavrilovic Collagen degradation and platelet-derived growth factor stimulate the migration of vascular smooth muscle cells J. Cell Sci., January 6, 2000; 113(11): 2055 - 2064. [Abstract] [PDF]
|
|
|
|
|
|
A Scherberich, M Campos-Toimil, P Ronde, K Takeda, and A Beretz Migration of human vascular smooth muscle cells involves serum-dependent repeated cytosolic calcium transients J. Cell Sci., January 2, 2000; 113(4): 653 - 662. [Abstract] [PDF]
|
|
|
|
 |
|
 X.-Q. Wang, F. P. Lindberg, and W. A. Frazier Integrin-associated Protein Stimulates {alpha}2{beta}1-dependent Chemotaxis via Gi-mediated Inhibition of Adenylate Cyclase and Extracellular-regulated Kinases J. Cell Biol., October 18, 1999; 147(2): 389 - 400. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Li, S. Sims, Y. Jiao, L. H. Chow, and J. G. Pickering Evidence From a Novel Human Cell Clone That Adult Vascular Smooth Muscle Cells Can Convert Reversibly Between Noncontractile and Contractile Phenotypes Circ. Res., August 20, 1999; 85(4): 338 - 348. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Brown, X. Pan, and A. Hassid Nitric Oxide and C-Type Atrial Natriuretic Peptide Stimulate Primary Aortic Smooth Muscle Cell Migration via a cGMP-Dependent Mechanism : Relationship to Microfilament Dissociation and Altered Cell Morphology Circ. Res., April 2, 1999; 84(6): 655 - 667. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Palmer, K. Tsoi, and D. H. Maurice Synergistic Inhibition of Vascular Smooth Muscle Cell Migration by Phosphodiesterase 3 and Phosphodiesterase 4 Inhibitors Circ. Res., May 4, 1998; 82(8): 852 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Li, L. H. Chow, and J. G. Pickering Cell Surface-bound Collagenase-1 and Focal Substrate Degradation Stimulate the Rear Release of Motile Vascular Smooth Muscle Cells J. Biol. Chem., November 3, 2000; 275(45): 35384 - 35392. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Li, Y.-S. Fan, L. H. Chow, C. Van Den Diepstraten, E. van der Veer, S. M. Sims, and J. G. Pickering Innate Diversity of Adult Human Arterial Smooth Muscle Cells: Cloning of Distinct Subtypes From the Internal Thoracic Artery Circ. Res., September 14, 2001; 89(6): 517 - 525. [Abstract] [Full Text] [PDF]
|
|