Are Rat Granulation Tissue Fibroblasts Regulated by Cytokines in the Same Manner as Skin Fibroblasts?

  • C. Maus
  • S. Gebauer
  • M. Bruns
  • K. Herrmann
  • U.-F. Haustein
Conference paper


The aim of the present study was to compare the collagen synthesis and proliferation of fibroblasts from human and rat skin with those from granulation tissue before and after incubation with transforming growth factor (31 (TGFβ) and interferon-gamma (IFNg). TGFβand IFNg are well-characterized cytokines that are able to regulate fibroblast metabolism. We showed that rat skin and human skin fibroblasts did not differ in proliferation or in their capacity to synthesize collagen. However, rat granulation tissue fibroblasts seemed to be in an activated state. Their proliferation and their collagen synthesis were significantly increased compared with normal rat skin and human skin fibroblasts. This effect was significant in 3-day-old granulation tissue fibroblasts. The effects of the cytokines TGFβand IFNg on collagen synthesis and proliferation differed quantitatively between skin and granulation tissue fibroblasts. In reaction to the cytokines used, day-3 granulation tissue fibroblasts produced the highest levels of collagen, followed by day-6 granulation tissue fibroblasts. Our findings support the idea of a time-dependent activation of granulation tissue fibroblasts.


Granulation Tissue Collagen Synthesis Skin Fibroblast Human Dermal Fibroblast Human Skin Fibroblast 
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  1. 1.
    Rodland K, Muldoon LL, Magun BE (1990) Cellular mechanism of TGFβ action. J Invest Dermatol 94: 33S - 40SPubMedCrossRefGoogle Scholar
  2. 2.
    Pierce GF, Mustoe GA, Lingelbach J, Masakowski VR, Griffin GL, Senior RM, Deuel TF (1989) Platelet-derived growth factor and transforming growth factor-ß enhance tissue repair activities by unique mechanisms. J Cell Biol 109: 429–440PubMedCrossRefGoogle Scholar
  3. 3.
    Clark RAF (1991) Cutaneous wound repair: a review with emphasis on integrin receptor expression. In: Janssen H, Rooman R, Robertson JIS (eds) Wound healing. Wirghtson:Google Scholar
  4. 4.
    Cromack DT, Sporn MB, Roberts AB, Merino MJ, Dart LL, Norton JA (1987) Transforming growth factor beta levels in rat wound chambers. J Surg Res 42: 622–628PubMedCrossRefGoogle Scholar
  5. 5.
    Mustoe TA, Pierce GF, Thomason A, Gramates P, Sporn MB, Deuel TF (1987) Accelerated healing of incisional wounds in rats induced by transforming growth factor-beta. Science 237: 1333–1336PubMedCrossRefGoogle Scholar
  6. 6.
    Wahl SM, Hunt DA, Wakefield LM, Mc-Cartney-Francis N, Wahl LM, Roberts AB, Sporn MB (1987) Transforming growth factor type beta induces monocyte Chemotaxis and growth factor production. Proc Natl Acad Sci USA 84: 5788–5792PubMedCrossRefGoogle Scholar
  7. 7.
    Rook AH, Kehrl JH, Wakefield LM, Roberts AB, Sporn MB, Burlington DB, Lane HC, Fauci AS (1986) Effects of transforming growth factor beta on the functions of natural killer cells: depressed cytolytic activity and blunting of interferon responsiveness. J Immunol 136: 3916–3920PubMedGoogle Scholar
  8. 8.
    Raghow R, Postlethwaite AE, Keski-Oja J, Moses HL, Kang AG (1987) Transforming growth factor-β increases steady-state levels of type-I procollagen and fibronectin messenger RNAs posttranscriptionally in cultured human dermal fibroblasts. J Clin Invest 79: 1285–1288PubMedCrossRefGoogle Scholar
  9. 9.
    Roberts AB, Sporn MB (1988) Transforming growth factor β. Adv Cancer Res 51: 107–145PubMedCrossRefGoogle Scholar
  10. 10.
    Overall C, Wrana JL, Sodek J (1989) Transforming growth factor-β regulation of collagenase, 72 kDa-progelatinase, TIMP and PAI-1 expression in rat bone cell populations and human fibroblasts. Connect Tiss Res 20: 289–294CrossRefGoogle Scholar
  11. 11.
    Duncan MR, Berman B (1989) Differential regulation of glycosaminoglycan, fibronectin and collagenase production in cultured human dermal fibroblasts by interferon- alpha, -beta, and -gamma. Arch Dermatol Res 281: 11–18PubMedCrossRefGoogle Scholar
  12. 12.
    Duncan MR, Berman B (1987) Persistence of a reduced-collagen-producing phenotype in cultured scleroderma fibroblasts after short-term exposure to interferons. J Clin Invest 79: 1318–1324PubMedCrossRefGoogle Scholar
  13. 13.
    Sato N, Nariuchi T, Tsuruoka N, Nishihara T, Beitz JG, Calabresi P, Frackelton AR jr (1990) Actions of TNF and IFNg on angiogenesis in vitro. J Invest Dermatol 95: 85S - 89SPubMedCrossRefGoogle Scholar
  14. 14.
    Scharffetter K, Heckmann M, Hatamochi A, Mauch C, Stein B, Riethmüller G, Ziegler-Heitbrock H-W, Krieg T (1989) Synergistic effect of tumor necrosis factor alpha and interferon-gamma on collagen synthesis of human skin fibroblasts in vitro. Exp Cell Res 181: 409–419PubMedCrossRefGoogle Scholar
  15. 15.
    Czaja MJ, Weiner FR, Eghbali ME, Giambrone M-A, Eghbali MA, Zern MA (1987) Differential effects of g-interferon on collagen and fibronectin gene expression. J Biol Chem 27: 13348–13351Google Scholar
  16. 16.
    Heckmann M, Aumailley M, Hatamochi A, Chu ML, Timpl R, Krieg T (1989) Down-regulation of alpha3 ( VI) chain expression by interferon gamma decreases synthesis and deposition of collagen.VI. Eur J Biochem 182: 719–726PubMedCrossRefGoogle Scholar
  17. 17.
    Adelmann-Grill BC, Hein R, Wach F, Krieg T (1987) Inhibition of fibroblasts Chemotaxis by recombinant human interferon gamma and interferon alpha. J Cell Physiol 130: 270–275PubMedCrossRefGoogle Scholar
  18. 18.
    Kulozik M, Heckmann M, Mauch C, Scharffetter K, Krieg T (1991) Cytokine regulation of collagen metabolism during wound healing in vitro and in vivo. In: Janssen H, Rooman R, Robertson JIS (eds) Wound healing. WirghtsonGoogle Scholar
  19. 19.
    Scharffetter K, Kulozik M, Stolz W, Lankat-Buttgereit B, Hatamochi A, Söhnchen R, Krieg T (1989) Localization of collagen al ( I) gene expression during wound healing by in situ hybridization. J Invest Dermatol 93: 405–412PubMedCrossRefGoogle Scholar
  20. 20.
    Kurkinen M, Vaheri A, Roberts P, Stenman S (1980) Sequential appearance of fibronectin and collagen in experimental granulation tissue. Lab Invest 43: 47–51PubMedGoogle Scholar
  21. 21.
    Clark RAF (1990) Fibronectin matrix deposition and fibronectin receptor expression in healing and normal skin. J Invest Dermatol 94: 128S - 134SPubMedCrossRefGoogle Scholar
  22. 22.
    White-Needleman B, Ordonez JV, Taramelli D, Alms W, Gayer K, Choi J (1990) In vitro identification of a subpopulation of fibroblasts that produces high levels of collagen in scleroderma patients. Arthritis Rheum 33: 842–849CrossRefGoogle Scholar
  23. 23.
    Mollenhauer J, Bayreuther K (1986) Donor-age-related changes in the morphology, growth potential, and collagen biosynthesis in rat fibroblast subpopulations in vitro. Differentiation 32: 165–172PubMedCrossRefGoogle Scholar
  24. 24.
    Bayreuther K, Rodemann HP, Francz PI, Maier K (1988) Differentiation of fibroblasts stem cells. J Cell Sci [Suppl] 10: 115–130Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • C. Maus
  • S. Gebauer
  • M. Bruns
  • K. Herrmann
  • U.-F. Haustein

There are no affiliations available

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