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Epidermal Growth Factor in Wound Healing: A Model for the Molecular Pathogenesis of Chronic Wounds

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Growth Factors and Wound Healing

Abstract

Wound healing in the skin is a complex biological process that has been extensively characterized at the light microscope level. However, regulation of skin wound healing is only partially understood at the molecular level. Skin wound healing can be divided into three general phases: (a) the inflammatory phase, (b) the repair phase, and (c) the remodeling phase. There is considerable temporal overlap of these stages of healing and the entire process lasts for several months (1, 2).

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References

  1. Bennett NT, Schultz GS. Growth factors and wound healing: biochemical properties of growth factors and their receptors. Am J Surg 1993;165:728–37.

    Article  PubMed  CAS  Google Scholar 

  2. Bennett NT, Schultz GS. Growth factors and wound healing: Part II. Role in normal and chronic wound healing. Am J Surg 1993;166:74–81.

    Article  PubMed  CAS  Google Scholar 

  3. Pierce GF, Mustoe TA, Altrock BW, Deuel TF, Thomason A. Role of platelet-derived growth factor in wound healing. J Cell Biochem 1991;45:319–26.

    Article  PubMed  CAS  Google Scholar 

  4. Karey KP, Sirbaska DA. Human platelet-derived mitogens, II. Subcellular localization of insulin-like growth factor I to the a-granule and release in response to thrombin. Blood 1989;74:1092–100.

    Google Scholar 

  5. Carpenter G, Cohen S. Epidermal growth factor. J Biol Chem 1990;265:7709–12.

    PubMed  CAS  Google Scholar 

  6. Border WA, Noble NA. Transforming growth factor β in tissue fibrosis. N Engl J Med 1994;10:1286–92.

    Google Scholar 

  7. Gadek JE, Fells GA, Wright DG, Crystal RG. Human neutrophil elastase functions as a type III collagen “collagenase.” Biochem Biophys Res Commun 1980;95:1815–22.

    Article  PubMed  CAS  Google Scholar 

  8. Morel F, Berthier S, Guillot M, et al. Human neutrophil gelatinase is a collagenase type IV. Biochem Biophys Res Commun 1993;191:269–74.

    Article  PubMed  CAS  Google Scholar 

  9. Hibbs MS, Hasty KA, Seyer JM, Kang AH, Mainardi CL. Biochemical and immunological characterization of the secreted forms of human neutrophil gelatinase. J Biol Chem 1985;260:2493–500.

    PubMed  CAS  Google Scholar 

  10. Ross R. The fibroblast and wound repair. Biol Rev 1968;43:51–96.

    Article  PubMed  CAS  Google Scholar 

  11. Kronke M, Schutze S, Scheurich P, Pfizenmaier K. In: Affarwal BB, Vilcek J, eds. Tumor necrosis factor: structure, function, and mechanism of action. New York: Marcel Dekker, 1995.

    Google Scholar 

  12. Vilcek J, Lee TH. Tumor necrosis factor. J Biol Chem 1991;266:7313–6.

    PubMed  CAS  Google Scholar 

  13. Ito A, Sato T, Iga T, Mori Y. Tumor necrosis factor bifunctionally regulates matrix metalloproteinases and tissue inhibitor of metalloproteinases (TIMP) production by human fibroblasts. Fed Exp Biol Sci 1990;269:93–5.

    CAS  Google Scholar 

  14. So T, Ito A, Sato T, Mori Y, Hirakawa S. Tumor necrosis factor-α stimulates the biosynthesis of matrix metalloproteinases and plasminogen activator in cultured human chorionic cells. Biol Rep 1992;46:772–8.

    Article  CAS  Google Scholar 

  15. Massague J. Transfroming growth factor-α. J Biol Chem 1990;265:21393–6.

    PubMed  CAS  Google Scholar 

  16. Shoyab M, Plowman GD, McDonald VL, Bradley GJ, Todaro GJ. Structure and function of human amphiregulin: a member of the epidermal growth factor family Science 1989;243:1074–6.

    CAS  Google Scholar 

  17. Higashiyama S, Abraham JA, Miller J, Fiddes JC, Klagsbrun M. A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF. Science 1991;251:936–9.

    Article  PubMed  CAS  Google Scholar 

  18. Ando Y, Jensen PJ. Epidermal growth factor and insulin-like growth factor I enhance keratinocyte migration. J Invest Dermatol 1993;100:633–9.

    Article  PubMed  CAS  Google Scholar 

  19. Ju WD, Schiller JT, Kazempour MK, Lowy DR. TGF-alpha enhances locomotion of cultured human keratinocytes. J Invest Dermatol 1993;100:628–32.

    PubMed  CAS  Google Scholar 

  20. Grant MB, Khaw PT, Schultz GS, Adams JL, Shimizu RW. Effects of epidermal growth factor, fibroblast growth factor and transforming growth factor-β on corneal cell chemotaxis. Invest Ophthalmol Vis Sci 1992; 33:3292–301.

    PubMed  CAS  Google Scholar 

  21. Grotendorst GR, Soma Y, Takehara K, Charette M. EGF and TGF-alpha are potent chemoattractants for endothelial cells and EGF-like peptides are present at sites of tissue regeneration. J Cell Physiol 1989;139:617–23.

    Article  PubMed  CAS  Google Scholar 

  22. Schreiber AB, Winkler ME, Derynck R. Transforming growth factor-α: a more potent angiogenic mediator than epidermal growth factor. Science 1986; 232:1250–3.

    Article  PubMed  CAS  Google Scholar 

  23. Buckley A, Davidson JM, Kamerath CD, Wolt TB, Woodward SC. Sustained release of epidermal growth factor accelerates wound repair. Proc Natl Acad Sci USA 1985;82:7340–4.

    Article  PubMed  CAS  Google Scholar 

  24. Coffey RJ, Derynck R, Wilcox JN, et al. Production and auto-induction of transforming growth factor-α in human keratinocytes. Nature 1987;328: 817–20.

    Article  PubMed  CAS  Google Scholar 

  25. Antoniades HN, Galanopoulos T, Neville-Golden J, Kiritsy CP, Lynch SE. Expression of growth factor and receptor mRNAs in skin epithelial cells following acute cutaneous injury. Am J Pathol 1993;142:1099–110.

    PubMed  CAS  Google Scholar 

  26. Wenczak BA, Lynch JB, Nanney LB. Epidermal growth factor receptor distribution in burn wounds. J Clin Invest 1990;90:2392–401.

    Article  Google Scholar 

  27. Todd R, Donoff BR, Chiang T, et al. Rapid communication: the eosinophil as a cellular source of transforming growth factor alpha in healing cutaneous wounds. Am J Pathol 1991;138:1307–13.

    PubMed  CAS  Google Scholar 

  28. Madtes DK, Raines EW, Sakariassen KS, et al. Induction of transforming growth factor-α in activated human alveolar macrophages. Cell 1988;53:285–93.

    Article  PubMed  CAS  Google Scholar 

  29. Rappolee DA, Mark D, Banda MJ, Werb Z. Wound macrophages express TGF-a and other growth factors in vivo: analysis by mRNA phenotyping. Science 1988;241:708–12.

    Article  PubMed  CAS  Google Scholar 

  30. Leibovich SJ, Ross R. The role of the macrophage in wound repair. Am J Pathol 1975;78:71–100.

    PubMed  CAS  Google Scholar 

  31. Mann GB, Fowler KJ, Gabriel A, Nice EC, Williams RL, Dunn AR. Mice with a null mutation of the TGF-a gene have abnormal skin architecture, wavy hair, and curly whiskers and often develop corneal inflammation. Cell 1993; 73:249–61.

    Article  PubMed  CAS  Google Scholar 

  32. Luetteke NC, Qiu TH, Peiffer RL, Oliver P, Smithies O, Lee DC. TGF-alpha deficiency results in hair follicle and eye abnormalities in targeted and waved-1 mice. Cell 1993;73:263–78.

    Article  PubMed  CAS  Google Scholar 

  33. Marikovsky M, Breuing K, Liu PY, et al. Appearance of heparin-binding EGF-like growth factor in wound fluid as a response to injury. Proc Natl Acad Sci USA 1993;90:3889–93.

    Article  PubMed  CAS  Google Scholar 

  34. Brown GB, Curtsinger L, Brightwell JR, et al. Enhancement of epidermal regeneration by biosynthetic epidermal growth factor. J Exp Med 1986; 163:1319–24.

    Article  PubMed  CAS  Google Scholar 

  35. Nanney LB. Epidermal and dermal effects of epidermal growth factor during wound repair. J Invest Dermatol 1990;94:624–9.

    Article  PubMed  CAS  Google Scholar 

  36. Lynch SE, Nixon JC, Colvin RB, Antoniades HN. Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors. Proc Natl Acad Sci USA 1987;84:7696–700.

    Article  PubMed  CAS  Google Scholar 

  37. Lynch SE, Colvin RB, Antoniades HN. Growth factors in wound healing: single and synergistic effects on partial thickness porcine skin wounds. J Clin Invest 1989;84:640–6.

    Article  PubMed  CAS  Google Scholar 

  38. Brown GL, Curtsinger LJ, White M, et al. Acceleration of tensile strength of incisions treated with EGF and TGF-beta. Ann Surg 1988;208:788–94.

    Article  PubMed  CAS  Google Scholar 

  39. Hennessey PJ, Black CT, Andrassy RJ. Epidermal growth factor and insulin act synergistically during diabetic healing. Arch Surg 1990;125:926–39.

    Article  PubMed  CAS  Google Scholar 

  40. Brown GL, Nanney LB, Griffen J, et al. Enhancement of wound healing by topical treatment with epidermal growth factor. N Engl J Med 1989;321:76–9.

    Article  PubMed  CAS  Google Scholar 

  41. Schultz GS, Chegini N, Grant MB, Khaw PT, MacKay S. Effects of growth factors on corneal wound healing. Acta Ophthalmol 1992;70:60–6.

    Google Scholar 

  42. Schultz GS, Khaw PT, Oxford K, Macauley S, Van Setten G, Chegini N. Growth factors and ocular wound healing. Eye 1994;8:184–7.

    Article  PubMed  Google Scholar 

  43. Schultz GS, Rotatori SD, Clark W. EGF and TGF-a in wound healing and repair. J Cell Biochem 1991;45:346–52.

    Article  PubMed  CAS  Google Scholar 

  44. Schultz GS, Grant MB. Neovascular growth factors. Eye 1991;5:170–80.

    Article  PubMed  Google Scholar 

  45. Leibowitz HM, Morello S, Stern M, Kupferman A. Effect of topically administered epidermal growth factor on corneal wound strength. Arch Ophthalmol 1990;108:734–7.

    Article  PubMed  CAS  Google Scholar 

  46. Brightwell JR, Riddle SL, Eiferman RA, et al. Biosynthetic human EGF accelerates healing on neodecadron-treated primate corneas. Invest Ophthalmol Vis Sci 1985;26:105–10.

    PubMed  CAS  Google Scholar 

  47. Brazzell RK, Stern ME, Aquavella JV, Beuerman RW, Baird L. Human recombinant epidermal growth factor in experimental corneal wound healing. Invest Ophthalmol Vis Sci 1991;32:336–40.

    PubMed  CAS  Google Scholar 

  48. Woost PG, Brightwell J, Eiferman RA, Schultz GS. Effect of growth factors with dexamethasone on healing of rabbit corneal stromal incisions. Exp Eye Res 1985;40:47–60.

    Article  PubMed  CAS  Google Scholar 

  49. Kandarakis AS, Page C, Kaufman HE. The effect of epidermal growth factor on epithelial healing after penetrating keratoplasty in human eyes. Am J Ophthalmol 1984;98:411–5.

    Article  PubMed  CAS  Google Scholar 

  50. Rich LF, Hatfield JM, Louiselle, I. The influence of epidermal growth factor on cat corneal endothelial wound healing. Curr Eye Res 1991;10:823–30.

    Article  PubMed  CAS  Google Scholar 

  51. Raphael B, Kerr NC, Shimizu RW, et al. Enhanced healing of cat corneal endothelial wounds by epidermal growth factor. Invest Ophthalmol Vis Sci 1993;34:2305–12.

    PubMed  CAS  Google Scholar 

  52. Pastor JC, Calonge M. Epidermal growth factor and corneal wound healing: a multicenter study. Cornea 1992;11:311–4.

    Article  PubMed  CAS  Google Scholar 

  53. Scardovi C, De Felice GP, Gazzaniga A. Epidermal growth factor in the topical treatment of traumatic corneal ulcers. Ophthalmologica 1993;206:119–24.

    Article  PubMed  CAS  Google Scholar 

  54. Falanga V, Eaglestein WH, Bucalo B, Katz MH, Harris B, Carson P. Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers. Phlebology 1992;18:604–6.

    CAS  Google Scholar 

  55. Chavira RJ, Burnett TJ, Hageman JH. Assaying proteinases with azocoll. Anal Biochem 1984;136:446–50.

    Article  PubMed  CAS  Google Scholar 

  56. Birkedal-Hansen H, Taylor RE. Detergent-activation of latent collagenase and resolution of its component molecules. Biochem Biophys Res Commun 1982;107:1173–8.

    Article  PubMed  CAS  Google Scholar 

  57. Tarnuzzer RW, Macauley SP, Farmerie WG, et al. Competitive RNA templates for detection and quantitation of growth factors, cytokines, extracellular matrix components and matrix metalloproteinases by RT-PCR. Biotechniques, in press.

    Google Scholar 

  58. Schultz GS, Strelow S, Stern GA, et al. Treatment of alkali-injured rabbit corneas with a synthetic inhibitor of matrix metalloproteinases. Invest Ophthalmol Vis Sci 1992;33:3325–31.

    PubMed  CAS  Google Scholar 

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Tarnuzzer, R.W. et al. (1997). Epidermal Growth Factor in Wound Healing: A Model for the Molecular Pathogenesis of Chronic Wounds. In: Ziegler, T.R., Pierce, G.F., Herndon, D.N. (eds) Growth Factors and Wound Healing. Serono Symposia USA Norwell, Massachusetts. Springer, New York, NY. https://doi.org/10.1007/978-1-4612-1876-0_12

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  • DOI: https://doi.org/10.1007/978-1-4612-1876-0_12

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4612-7321-9

  • Online ISBN: 978-1-4612-1876-0

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