Endogenous Growth Factor Pathways May Regulate Epidermal Hyperplasia in Chronic Venous Wounds: Modulation by Hydrocolloid Dressings

  • J. G. Krueger
  • L. Staiano-Coico
  • B. Smoller
  • M. Anzilotti
  • V. P. Vallat
  • P. Gilleaudeau
  • A. B. Gottlieb

Abstract

While qualitative aspects of dermal repair differ in wounds of different types, duration, and depths, all wounds must be resurfaced by epidermal keratinocytes before they can be deemed “healed.” Epidermal keratinocytes undergo a series of activation steps in acute wound healing, which are likely to be regulated by autocrine growth control mechanims. The state of epidermal keratinocyte activation in chronic venous wounds is examined in this study in relationship to the correct expression of these changes in acute wound healing. The expression of endogenous growth factor pathways in chronic wounds is presented and changes in the growth activation associated with healing of chronic wounds are studied. The results of this study establish that growth activation of the epidermis is not defective in chronic wounds. The activation of epidermis is likely to be regulated by endogenous keratinocyte cytokine and receptor pathways, suggesting that addition of exogenous epidermal mitogens to chronic wounds is unlikely to further alter epidermal healing. In contrast, some of the therapeutic benefits of hydrocolloid dressings in promoting healing of chronic wounds may be related to their ability to suppress excessive keratinocyte proliferation and activation in chronic wounds.

Keywords

Migration Tyrosine Heparin Oncol Polypeptide 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Mansbridge JN, Knapp AM (1987) Changes in keratinocyte maturation during wound healing. J Invest Dermatol 89:253–263.PubMedCrossRefGoogle Scholar
  2. 2.
    Krawczyk WS (1971) A pattern of epidermal cell migration during wound healing. J Cell Biol 49:247–263.PubMedCrossRefGoogle Scholar
  3. 3.
    Washburn WW Jr (1954) Comparative histochemical observations on wound healing in adult rats and cultured adult human epithelium. II. Ribonucleic acid and thymonucleic acid. J Invest Dermatol 23:169–179.PubMedCrossRefGoogle Scholar
  4. 4.
    Rovee DT, Kurowsky CA, Labun J (1972) Local wound environment and epidermal healing. Mitotic response. Arch Dermatol 106:330–334.PubMedCrossRefGoogle Scholar
  5. 5.
    Hertle MD, Kubier M-D, Leigh IM, Watt FM (1992) Aberrant integrin expression during epidermal wound healing and in psoriatic epidermis. J Clin Invest 89:1892–1901.PubMedCrossRefGoogle Scholar
  6. 6.
    Woodley DT, Peterson HD, Herzog SR, Stricklin GP, Burgeson RE, Briggaman RA, Cronce DJ, O’Keefe EJ (1988) Burn wounds resurfaced by cultured epidermal autografts show abnormal reconstitution of anchoring fibrils. JAMA 259:2566–2571.PubMedCrossRefGoogle Scholar
  7. 7.
    Clark RAF (1985) Cutaneous tissue repair: basic biologic considerations. I. J Amer Acad Dermatol 13:701–725.CrossRefGoogle Scholar
  8. 8.
    Fisher LB, Maibach HI (1972) The effect of occlusive and semipermeable dressings on the mitotic activity of normal and wounded human epidermis. Br J Dermatol 86:593–600.PubMedCrossRefGoogle Scholar
  9. 9.
    Fisher DA, Lakshmanan J (1990) Metabolism and effects of epidermal growth factor and related growth factors in mammals. Endocr Rev 11:418–442.PubMedCrossRefGoogle Scholar
  10. 10.
    Krane JF, Murphy DP, Carter DM, Krueger JG (1991) Synergistic effects of epidermal growth factor (EGF) and insulin-like growth factor I/somatomedin C (IGF-I) on keratinocyte proliferation may be mediated by IGF-I transmodulation of the EGF receptor. J Invest Dermatol 96:419–424.PubMedCrossRefGoogle Scholar
  11. 11.
    Gospodarowicz D, Plouët J, Malerstein B (1990) Comparison of the ability of basic and acidic fibroblast growth factor to stimulate the proliferation of an established keratinocyte cell line: modulation of their biological effects by heparin, transforming growth factor β (TGFβ), and epidermal growth factor (EGF). J Cell Physiol 142:325–333.PubMedCrossRefGoogle Scholar
  12. 12.
    Marchese C, Rubin J, Ron D, Faggioni A, Torrisi MR, Messina A, Frati L, Aaronson SA (1990) Human keratinocyte growth factor activity on proliferation and differentiation of human keratinocytes: differentiation response distinguishes KGF from EGF family. J Cell Physiol 144:326–332.PubMedCrossRefGoogle Scholar
  13. 13.
    Uyttendaele HI, Krane JF, Gottlieb AB, Krueger JG (1992) Identification of the bFGF receptor and mitogenic response pathways in keratinocytes and human skin. J Invest Dermatol 98:611.Google Scholar
  14. 14.
    Ansel JC, Tara DC, Krueger J, Olerud J, Hart C (1992) Selective regulation and secretion of keratinocyte PDGF isoforms: implications for cutaneous bioactivity. J Invest Dermatol 98:565.Google Scholar
  15. 15.
    Krueger JG, Krane JF, Carter DM, Gottlieb AB (1990) Role of growth factors, cytokines, and their receptors in the pathogenesis of psoriasis. J Invest Dermatol 94:135S–140S.PubMedCrossRefGoogle Scholar
  16. 16.
    Kaplan G, Walsh G, Guido LS, Meyn P, Burkhardt RA, Abalos RM, Barker J, Frindt PA, Fajardo TT, Cohn ZA (1992) Novel responses of human skin to intradermal recombinant granulocyte/macrophage-colony-stimulating factor: Langerhans cell recruitment, keratinocyte growth, and enhanced wound healing. J Exp Med 175:1717–1728.PubMedCrossRefGoogle Scholar
  17. 17.
    Lynch SE, Colvin RB, Antoniades HN (1989) Growth factors in wound healing. Single and synergistic effects on partial thickness porcine skin wounds. J Clin Invest 84:640–646.PubMedCrossRefGoogle Scholar
  18. 18.
    Grotendorst GR (1988) Growth factors as regulators of wound repair. Int J Tissue React X:337–344.Google Scholar
  19. 19.
    Deuel TF, Kawahara RS, Mustoe TA, Pierce GF (1991) Growth factors and wound healing: platelet-derived growth factor as a model cytokine. Annu Rev Med 42:567–584.PubMedCrossRefGoogle Scholar
  20. 20.
    Coffey RJ Jr, Derynck R, Wilcox JN, Bringman TS, Goustin AS, Moses HL, Pittelkow MR (1987) Production and auto-induction of transforming growth factor-α in human keratinocytes. Nature 328:817–823.PubMedCrossRefGoogle Scholar
  21. 21.
    Gottlieb AB, Chang CK, Posnett DN, Fanelli B, Tarn JP (1988) Detection of transforming growth factor (alpha) in normal, malignant, and hyperproliferative human keratinocytes. J Exp Med 167:670–675.PubMedCrossRefGoogle Scholar
  22. 22.
    Nanney LB, Stoscheck CM, Magid M, King LE (1986) Altered epidermal growth factor binding and receptor distribution in psoriasis. J Invest Dermatol 86:260–265.PubMedCrossRefGoogle Scholar
  23. 23.
    Krane JF, Gottlieb AB, Carter DM, Krueger JG (1992) The insulin-like growth factor I receptor is overexpressed in psoriatic epidermis, but is differentially regulated from the epidermal growth factor receptor. J Exp Med 175:1081–1090.PubMedCrossRefGoogle Scholar
  24. 24.
    Grossman RM, Krueger J, Yourish D, Granelli-Piperno A, Murphy DP, May LT, Kupper TS, Sehgal PB, Gottlieb AB (1989) Interleukin 6 is expressed in high levels in psoriatic skin and stimulates proliferation of cultured human keratinocytes. Proc Natl Acad Sci USA 86:6367–6371.PubMedCrossRefGoogle Scholar
  25. 25.
    Kupper TS (1990) Immune and inflammatory processes in cutaneous tissues. Mechanisms and speculations. J Clin Invest 86:1783–1789.PubMedCrossRefGoogle Scholar
  26. 26.
    Werner S, Peters KG, Longaker MT, Fuller-Pace F, Banda MJ, Williams LT (1992) Large induction of keratinocyte growth factor expression in the dermis during wound healing. Proc Natl Acad Sci USA 89:6896–6900.PubMedCrossRefGoogle Scholar
  27. 27.
    Krane JF, Murphy DP, Gottlieb AB, Carter DM, Hart CE, Krueger JG (1991) Increased dermal expression of platelet-derived growth factor receptors in growth-activated skin wounds and psoriasis. J Invest Dermatol 96:983–986.PubMedCrossRefGoogle Scholar
  28. 28.
    Bruno S, Darzynkiewicz Z (1992) Cell cycle dependent expression and stability of the nuclear protein detected by Ki-67 antibody in HL-60 cells. Cell Prolif 25:31–40.PubMedCrossRefGoogle Scholar
  29. 29.
    Nemeth AJ, Eaglstein WH, Taylor JR, Peerson LJ, Falanga V (1991) Faster healing and less pain in skin biopsy sites treated with an occlusive dressing. Arch Dermatol 127:1679–1683.PubMedCrossRefGoogle Scholar
  30. 30.
    Bolton L, van Rijswijk L (1991) Wound dressings: meeting clinical and biological needs. Dermatol Nurs 3:146–160.PubMedGoogle Scholar
  31. 31.
    Madden MR, Nolan E, Finkelstein JL, Yurt RW, Smeland J, Goodwin CW, Hefton J, Staiano-Coico L (1989) Comparison of an occlusive and a semi-occlusive dressing and the effect of the wound exudate upon keratinocyte proliferation. J Trauma 29:924–930.PubMedCrossRefGoogle Scholar
  32. 32.
    Gottlieb AB, Staiano-Coico L, Cohen SR, Varghese M, Carter DM (1990) Occlusive hydrocolloid dressings decrease keratinocyte population growth fraction and clinical scale and skin thickness in active psoriatic plaques. J Dermatol Sci 1:93–96.PubMedCrossRefGoogle Scholar
  33. 33.
    Woodley DT, O’Keefe EJ, Prunieras M (1985) Cutaneous wound healing: a model for cell-matrix interactions. J Am Acad Dermatol 12:420–433.PubMedCrossRefGoogle Scholar
  34. 34.
    Grinnell F, Toda K-I, Takashima A (1988) Role of fibronectin in epithelialization and wound healing. In: Hunt T et al. (eds) Growth factors and other aspects of wound healing: biological and clinical implications. Liss, New York, pp 259–272.Google Scholar
  35. 35.
    Clark RAF (1988) Potential roles of fibronectin in cutaneous wound repair. Arch Dermatol 124:201–206.PubMedCrossRefGoogle Scholar
  36. 36.
    Falanga V, Eaglstein WH, Bucalo B, Katz MH, Harris B, Carson P (1992) Topical use of human recombinant epidermal growth factor (h-EGF) in venous ulcers. J Dermatol Surg Oncol 18:604–606.PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • J. G. Krueger
    • 1
  • L. Staiano-Coico
    • 2
  • B. Smoller
    • 3
  • M. Anzilotti
    • 1
  • V. P. Vallat
    • 1
  • P. Gilleaudeau
    • 1
  • A. B. Gottlieb
    • 1
  1. 1.The Rockefeller UniversityNew YorkUSA
  2. 2.Medical CollegeCornell UniversityNew YorkUSA
  3. 3.Stanford University School of MedicinePalo AltoUSA

Personalised recommendations