Crossref journal-article
Ovid Technologies (Wolters Kluwer Health)
Circulation Research (276)
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.

Bibliography

Pickering, J. G., Uniyal, S., Ford, C. M., Chau, T., Laurin, M. A., Chow, L. H., Ellis, C. G., Fish, J., & Chan, B. M. C. (1997). Fibroblast Growth Factor-2 Potentiates Vascular Smooth Muscle Cell Migration to Platelet-Derived Growth Factor. Circulation Research, 80(5), 627–637.

Authors 9
  1. J. Geoffrey Pickering (first)
  2. Shashi Uniyal (additional)
  3. Carol M. Ford (additional)
  4. Thu Chau (additional)
  5. Mary Ann Laurin (additional)
  6. Lawrence H. Chow (additional)
  7. Christopher G. Ellis (additional)
  8. Jonathan Fish (additional)
  9. Bosco M. C. Chan (additional)
References 62 Referenced 57
  1. 10.1038/362801a0
  2. 10.1161/circ.86.3.1516183
  3. 10.1002/jcp.1041130213
  4. 10.1016/0012-1606(91)90074-D
  5. 10.1083/jcb.122.3.729
  6. 10.1172/JCI117764
  7. 10.1172/JCI117962
  8. 10.1016/S0092-8674(00)81281-7
  9. 10.1016/S0092-8674(00)81279-9
  10. 10.1161/res.78.4.596
  11. 10.1161/atvb.16.1.28
  12. 10.1161/res.75.1.8013081
  13. Gospodarowicz D. Fibroblast growth factor. Crit Rev Oncog. 1989;1:1-26. / Crit Rev Oncog (1989)
  14. 10.1161/res.68.1.1984855
  15. 10.1073/pnas.88.9.3739
  16. Jackson CL, Reidy MA. Basic fibroblast growth factor: its role in the control of smooth muscle cell migration. Am J Pathol. 1993;143:1024-1031. / Am J Pathol (1993)
  17. 10.1126/science.1653454
  18. 10.1172/JCI118236
  19. 10.1016/0092-8674(92)90115-S
  20. 10.1161/res.67.1.1694736
  21. 10.1161/01.ATV.10.3.402
  22. 10.1083/jcb.111.5.2159
  23. 10.1111/j.1432-0436.1989.tb00743.x
  24. 10.1161/res.76.2.209
  25. Skinner MP, Raines EW, Ross R. Dynamic expression of α1β1 and α2β2 integrin receptors by human vascular smooth muscle cells: α2β1 integrin is required for chemotaxis across type I collagen coated membranes. Am J Pathol. 1994;145:1070-1081. / Am J Pathol (1994)
  26. 10.1016/0014-4827(92)90173-6
  27. 10.1006/excr.1994.1282
  28. Koyama N, Seki J, Vergel S, Mattsson EJ, Harlan JM, Clowes AW. Regulation and function of an activation-dependent epitope of the β1 integrins in vascular cells after balloon injury in baboon arteries and in vitro. Am J Pathol. 1996;148:749-761. / Am J Pathol (1996)
  29. 10.1002/jcp.1041510319
  30. 10.1002/jcp.1041530116
  31. 10.1091/mbc.4.10.973
  32. 10.4049/jimmunol.132.6.3011
  33. Hangan D, Uniyal S, Morris V, MacDonald I, von Ballestrem C, Chau T, Schmidt E, Chambers A, Groom A, Chan BMC. Integrin VLA-2 (α2β1) function in post-extravasation movement of human rhabdomyosarcoma cells in the liver. Cancer Res. 1996;56:3142-3149. / Cancer Res (1996)
  34. 10.1073/pnas.76.3.1274
  35. 10.1016/0076-6879(82)82103-4
  36. 10.1016/0735-1097(92)90259-P
  37. 10.1172/JCI116254
  38. 10.1016/0092-8674(90)90661-W
  39. 10.1016/S0021-9258(18)42453-2
  40. 10.1073/pnas.78.6.3669
  41. 10.1016/0092-8674(92)90077-P
  42. 10.1016/0006-291X(91)91557-S
  43. Clowes A, Reidy M, Clowes M. Kinetics of cellular proliferation after arterial injury, I: smooth muscle growth in the absence of endothelium. Lab Invest. 1983;49:327-333. / Lab Invest (1983)
  44. 10.1161/res.74.3.8118957
  45. 10.1172/JCI118693
  46. Mechtersheimer G, Barth T, Quentmeier A, Moller P. Differential expression of β1 integrins in nonneoplastic smooth and striated muscle cells and in tumors derived from these cells. Am J Pathol. 1994;144:1172-1182. / Am J Pathol (1994)
  47. 10.1242/jcs.102.3.437
  48. 10.1242/jcs.108.2.595
  49. 10.1016/S0006-3495(91)82027-6
  50. Humphries MJ Mould AP Yamada KM. Matrix receptors in cell migration. In: Mecham R ed. Receptors for Extracellular Matrix. New York NY: Academic Press Inc; 1991. (10.1016/B978-0-12-483365-4.50011-6)
  51. 10.1016/0012-1606(82)90155-5
  52. Hay ED, Revel JP. Fine structure of the developing avian cornea. Monogr Dev Biol. 1969;1:1-144. / Monogr Dev Biol (1969)
  53. Walpola PL, Gotlieb AI, Langille BL. Monocyte adhesion and changes in endothelial cell number, morphology, and F-actin distribution elicited by low shear stress in vivo. Am J Pathol. 1993;142:1392-1400. / Am J Pathol (1993)
  54. 10.1083/jcb.134.6.1551
  55. 10.1083/jcb.131.6.1857
  56. 10.1161/atvb.17.3.475
  57. 10.1083/jcb.131.6.1903
  58. 10.1016/0092-8674(92)90163-7
  59. 10.1016/0092-8674(95)90370-4
  60. 10.1016/S0021-9258(17)42406-9
  61. 10.1016/S0741-5214(94)70127-X
  62. 10.1161/circ.90.5.7955174
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)
Funders 0

None

@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} }