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J Cell Biol. Aug 1, 1989; 109(2): 811–822.
PMCID: PMC2115699

Growth factors are released by mechanically wounded endothelial cells

Abstract

Growth factors may be required at sites of mechanical injury and normal wear and tear in vivo, suggesting that the direct action of mechanical forces on cells could lead to growth factor release. Scraping of cells from the tissue culture substratum at 37 degrees C was used to test this possibility. We show that scraping closely mimics in vitro both the transient plasma membrane wounds observed in cells subject to mechanical forces in vivo (McNeil, P. L., and S. Ito. 1989. Gastroenterology. 96:1238-1248) and the transient plasma membrane wounds shown here to occur in endothelial cells under normal culturing conditions. Scraping of endothelial cells from the culturing substratum released into the culture medium a potent growth-promoting activity for Swiss 3T3 fibroblasts. Growth-promoting activity was released rapidly (within 5 min) after scraping but was not subsequently degraded by the endothelial cells for at least 24 h thereafter. A greater quantity of growth-promoting activity was released by cells scraped 4 h after plating than by those scraped 4 or 7 d afterwards. Thus release is not due to scraping-induced disruption of extracellular matrix. Release was only partially cold inhibitable, was poorly correlated with the level of cell death induced by scraping, and did not occur when cells were killed with metabolic poisons. These results suggest that mechanical disruption of plasma membrane, either transient or permanent, is the essential event leading to release. A basic fibroblast growth factor- like molecule and not platelet-derived growth factor appears to be partially responsible for the growth-promoting activity. We conclude that one biologically relevant route of release of basic fibroblast growth factor, a molecule which lacks the signal peptide sequence for transport into the endoplasmic reticulum, could be directly through mechanically induced membrane disruptions of endothelial cells growing in vivo and in vitro.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • ABERCROMBIE M. Localized formation of new tissue in an adult mammal. Symp Soc Exp Biol. 1957;11:235–254. [PubMed]
  • Abraham JA, Mergia A, Whang JL, Tumolo A, Friedman J, Hjerrild KA, Gospodarowicz D, Fiddes JC. Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. Science. 1986 Aug 1;233(4763):545–548. [PubMed]
  • Adams JC. Technical considerations on the use of horseradish peroxidase as a neuronal marker. Neuroscience. 1977;2(1):141–145. [PubMed]
  • Auron PE, Webb AC, Rosenwasser LJ, Mucci SF, Rich A, Wolff SM, Dinarello CA. Nucleotide sequence of human monocyte interleukin 1 precursor cDNA. Proc Natl Acad Sci U S A. 1984 Dec;81(24):7907–7911. [PMC free article] [PubMed]
  • Beckers CJ, Keller DS, Balch WE. Semi-intact cells permeable to macromolecules: use in reconstitution of protein transport from the endoplasmic reticulum to the Golgi complex. Cell. 1987 Aug 14;50(4):523–534. [PubMed]
  • Bertsch S, Csontos K, Schweizer J, Marks F. Effect of mechanical stimulation on cell proliferation in mouse epidermis and on growth regulation by endogenous factors (chalones). Cell Tissue Kinet. 1976 Sep;9(5):445–457. [PubMed]
  • DiCorleto PE. Cultured endothelial cells produce multiple growth factors for connective tissue cells. Exp Cell Res. 1984 Jul;153(1):167–172. [PubMed]
  • DiCorleto PE, Gajdusek CM, Schwartz SM, Ross R. Biochemical properties of the endothelium-derived growth factor: comparison to other growth factors. J Cell Physiol. 1983 Mar;114(3):339–345. [PubMed]
  • Folkman J, Klagsbrun M, Sasse J, Wadzinski M, Ingber D, Vlodavsky I. A heparin-binding angiogenic protein--basic fibroblast growth factor--is stored within basement membrane. Am J Pathol. 1988 Feb;130(2):393–400. [PMC free article] [PubMed]
  • Gitlin JD, D'Amore PA. Culture of retinal capillary cells using selective growth media. Microvasc Res. 1983 Jul;26(1):74–80. [PubMed]
  • Gospodarowicz D, Moran J, Braun D, Birdwell C. Clonal growth of bovine vascular endothelial cells: fibroblast growth factor as a survival agent. Proc Natl Acad Sci U S A. 1976 Nov;73(11):4120–4124. [PMC free article] [PubMed]
  • Jaye M, Howk R, Burgess W, Ricca GA, Chiu IM, Ravera MW, O'Brien SJ, Modi WS, Maciag T, Drohan WN. Human endothelial cell growth factor: cloning, nucleotide sequence, and chromosome localization. Science. 1986 Aug 1;233(4763):541–545. [PubMed]
  • Klagsbrun M, Shing Y. Heparin affinity of anionic and cationic capillary endothelial cell growth factors: analysis of hypothalamus-derived growth factors and fibroblast growth factors. Proc Natl Acad Sci U S A. 1985 Feb;82(3):805–809. [PMC free article] [PubMed]
  • Lemasters JJ, DiGuiseppi J, Nieminen AL, Herman B. Blebbing, free Ca2+ and mitochondrial membrane potential preceding cell death in hepatocytes. Nature. 1987 Jan 1;325(6099):78–81. [PubMed]
  • Lobb RR, Harper JW, Fett JW. Purification of heparin-binding growth factors. Anal Biochem. 1986 Apr;154(1):1–14. [PubMed]
  • Lomedico PT, Gubler U, Hellmann CP, Dukovich M, Giri JG, Pan YC, Collier K, Semionow R, Chua AO, Mizel SB. Cloning and expression of murine interleukin-1 cDNA in Escherichia coli. Nature. 312(5993):458–462. [PubMed]
  • Mcneil PL. Incorporation of macromolecules into living cells. Methods Cell Biol. 1989;29:153–173. [PubMed]
  • McNeil PL, Ito S. Gastrointestinal cell plasma membrane wounding and resealing in vivo. Gastroenterology. 1989 May;96(5 Pt 1):1238–1248. [PubMed]
  • McNeil PL, Warder E. Glass beads load macromolecules into living cells. J Cell Sci. 1987 Dec;88(Pt 5):669–678. [PubMed]
  • McNeil PL, Murphy RF, Lanni F, Taylor DL. A method for incorporating macromolecules into adherent cells. J Cell Biol. 1984 Apr;98(4):1556–1564. [PMC free article] [PubMed]
  • Revel JP. Contacts and junctions between cells. Symp Soc Exp Biol. 1974;(28):447–461. [PubMed]
  • Sato Y, Rifkin DB. Autocrine activities of basic fibroblast growth factor: regulation of endothelial cell movement, plasminogen activator synthesis, and DNA synthesis. J Cell Biol. 1988 Sep;107(3):1199–1205. [PMC free article] [PubMed]
  • Schwane JA, Armstrong RB. Effect of training on skeletal muscle injury from downhill running in rats. J Appl Physiol Respir Environ Exerc Physiol. 1983 Sep;55(3):969–975. [PubMed]
  • Schweigerer L, Neufeld G, Friedman J, Abraham JA, Fiddes JC, Gospodarowicz D. Capillary endothelial cells express basic fibroblast growth factor, a mitogen that promotes their own growth. Nature. 1987 Jan 15;325(6101):257–259. [PubMed]
  • Swanson JA, McNeil PL. Nuclear reassembly excludes large macromolecules. Science. 1987 Oct 23;238(4826):548–550. [PubMed]
  • Thomas KA. Transforming potential of fibroblast growth factor genes. Trends Biochem Sci. 1988 Sep;13(9):327–328. [PubMed]
  • Vlodavsky I, Fridman R, Sullivan R, Sasse J, Klagsbrun M. Aortic endothelial cells synthesize basic fibroblast growth factor which remains cell associated and platelet-derived growth factor-like protein which is secreted. J Cell Physiol. 1987 Jun;131(3):402–408. [PubMed]
  • Walter P, Lingappa VR. Mechanism of protein translocation across the endoplasmic reticulum membrane. Annu Rev Cell Biol. 1986;2:499–516. [PubMed]
  • Warhol MJ, Siegel AJ, Evans WJ, Silverman LM. Skeletal muscle injury and repair in marathon runners after competition. Am J Pathol. 1985 Feb;118(2):331–339. [PMC free article] [PubMed]
  • Wright HP. Endothelial mitosis around aortic branches in normal guinea pigs. Nature. 1968 Oct 5;220(5162):78–79. [PubMed]
  • Young PR, Hazuda DJ, Simon PL. Human interleukin 1 beta is not secreted from hamster fibroblasts when expressed constitutively from a transfected cDNA. J Cell Biol. 1988 Aug;107(2):447–456. [PMC free article] [PubMed]

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