Abstract
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 β 1 integrin–mediated interactions with the extracellular matrix (ECM). FGF-2 significantly increased surface expression of α 2 β 1 , α 3 β 1 , and α 5 β 1 integrins on human SMCs, as assessed by flow cytometry. The greatest increase was for the collagen-binding α 2 β 1 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-α 2 β 1 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 α-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 α 2 β 1 integrin; and (3) FGF-2 disassembles actin stress fibers, which may promote differential utilization of α 2 β 1 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.
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Dates
Type | When |
---|---|
Created | 13 years, 2 months ago (June 11, 2012, 8:47 p.m.) |
Deposited | 1 year, 3 months ago (May 12, 2024, 4:56 p.m.) |
Indexed | 2 months, 2 weeks ago (June 14, 2025, 11:46 a.m.) |
Issued | 28 years, 3 months ago (May 1, 1997) |
Published | 28 years, 3 months ago (May 1, 1997) |
Published Print | 28 years, 3 months ago (May 1, 1997) |
@article{Pickering_1997, title={Fibroblast Growth Factor-2 Potentiates Vascular Smooth Muscle Cell Migration to Platelet-Derived Growth Factor: Upregulation of α 2 β 1 Integrin and Disassembly of Actin Filaments}, volume={80}, ISSN={1524-4571}, url={http://dx.doi.org/10.1161/01.res.80.5.627}, DOI={10.1161/01.res.80.5.627}, number={5}, journal={Circulation Research}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Pickering, J. Geoffrey and Uniyal, Shashi and Ford, Carol M. and Chau, Thu and Laurin, Mary Ann and Chow, Lawrence H. and Ellis, Christopher G. and Fish, Jonathan and Chan, Bosco M. C.}, year={1997}, month=may, pages={627–637} }