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Tissue Repair and Fibrosis pp 35–45Cite as

Transforming Growth Factor-β Gene Transfer to the Lung Induces Myofibroblast Presence and Pulmonary Fibrosis

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Part of the book series: Current Topics in Pathology ((CT PATHOLOGY,volume 93))

Abstract

Many cytokines have been implicated in the initiation or propagation of fibrogenesis. In particular, the early-phase inflammatory cytokines, interleukin (IL) and tumor necrosis factor (TNF), and members of the chemokine families, including IL and monocyte chemotactic peptide (MCP-1) are known to be present in inflamed tissue, both at the beginning and at advanced stages of fibrosis. In addition, growth and differentiating factors, such as the fibroblast growth factors (FGFs), transforming growth factors (TGFs) and platelet-derived growth factors (PDGFs) are all implicated in the pathogenesis of fibrosis through their putative mode of action and demonstrated presence in fibrotic tissue. Most data implicating the various cytokines arises from studies involving immunohistochemistry or detection of gene expression within fibrotic tissue and from in vitro experiments showing activity on matrix formation by structural cells (fibroblasts, smooth-muscle cells, etc.).

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References

  1. Braciak TA, Bacon K, Xing Z et al. (1996) Overexpression of RANTES using a recombinant adenovirus vector induces the tissue-directed recruitment of monocytes to the lung. J Immunol 157:5076–5084

    PubMed  CAS  Google Scholar 

  2. Bramson JL, Graham FL, Gauldie J (1995) The use of adenoviral vectors for gene therapy and gene transfer in vivo. Curr Opin Biotechnol 6:590–595

    Article  PubMed  CAS  Google Scholar 

  3. Broekelmann TJ, Limper AH, Colvy TV, McDonald JA (1991) Transforming growth factor 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis. Proc Natl Acad Sci U S A 88:6642–6646

    Article  PubMed  CAS  Google Scholar 

  4. Brunner Am, Marquardt H, Malacko AR, Lioubin MN, Purchio AF (1989) Site-directed mutagenesis of cysteine residues in the pro region of the transforming growth factor 1 precursor: expression and characterization of mutant proteins. J Biol Chem 264:13660–13664

    PubMed  CAS  Google Scholar 

  5. Darby I, Skalli O, Gabbiani G (1990) Smooth muscle actin is transiently expressed by myofibroblasts during experimental wound healing. Lab Invest 63:21–29

    PubMed  CAS  Google Scholar 

  6. Dedhar S, Gaboury L, Galloway P, Eaves C (1988) Human granulocyte-macrophage colony-stimulating factor is growth factor active on a variety of cell types of non-hemopoietic origin. Proc Natl Acad Sci U S A 85:9253–9257

    Article  PubMed  CAS  Google Scholar 

  7. Desmouliere A (1995) Factors influencing myofibroblast differentiation during wound healing and fibrosis. Cell Biol Int 19:471–476

    Article  PubMed  CAS  Google Scholar 

  8. Desmoulière A, Geinoz A, Gabbiani F, Gabbiani G (1993) Transforming growth factor-βl induces a-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 122:103–111

    Article  PubMed  Google Scholar 

  9. Foley R, Driscoll K, Wan Y, Braciak T, Howard B, Xing Z, Graham F, Gauldie J (1995) Adenoviral gene transfer of macrophage inflammatory protein-2 in rat lung. Am J Pathol 149: 1395–1403

    Google Scholar 

  10. Gauldie J, Jordana M, Cox G(1993) Cytokines and pulmonary fibrosis. Thorax 48:931–935

    Article  PubMed  CAS  Google Scholar 

  11. Glasser SW, Korfhagen TR, West SE, Whitsett JA (1994) Transgenic models for study of pulmonary development and disease. Am J Physiol 267:L489–L497

    PubMed  CAS  Google Scholar 

  12. Kapanci Y, Desmouliere A, Pache J-C, Redard M, Gabbiani G (1995) Cytoskeletal protein modulation in pulmonary alveolar myofibroblasts during idiopathic pulmonary fibrosis: possible role of TGF-β and TNF-α. Am J Respir Crit Care Med 152:2163–2169

    PubMed  CAS  Google Scholar 

  13. Khalil N, Whitman C, Danielpour D, Greenberg A (1993) Regulation of alveolar macrophage transforming growth factor-β secretion by corticosteroids in bleomycin-induced pulmonary inflammation in the rat. J Clin Invest 92:1812–1818

    Article  PubMed  CAS  Google Scholar 

  14. Khalil N, O’Conner RN, Flanders KC, Umruh H (1996) TGF-βl, but not TGF-β2 or TGF-β3, is differentially present in epithelial cells of advanced pulmonary fibrosis: an immunohistochemical study. Am J Respir Cell Mol Biol 14:131–138

    PubMed  CAS  Google Scholar 

  15. Khalil N, Corne S, Whitman C, Yacyshyn H (1996) Plasmin regulates the activation of cell-associated latent TGF-βl secreted by rat alveolar macrophages after in vivo bleomycin injury. Am J Respir Cell Mol Biol 15:252–259

    PubMed  CAS  Google Scholar 

  16. Lyons RM, Keski-Oja J, Moses HL (1988) Proteolytic activation of latent transforming growth factor-β from fibroblast-conditioned medium. Eur J Biochem 1990:1659–1665

    Google Scholar 

  17. Lyons RM, Gentry LE, Purchio AF et al. (1990) Mechanism of activation of latent recombinant TGFβ1 by plasmin. J Cell Biol 110:1361–1367

    Article  PubMed  CAS  Google Scholar 

  18. Miyazaki Y, Araki K, Vesin C, Garcia I, Kapanci Y, Whitsett JA, Piguet P-F, Vassalli P (1995) Expression of a tumor necrosis factor-transgene in murine lung causes lymphocytic and fibrosing alveolitis. J Clin Invest 96:250–259

    Article  PubMed  CAS  Google Scholar 

  19. Phan SH, Kunkel SL (1992) Lung cytokine production in bleomycin-induced pulmonary fibrosis. Exp Lung Res 18:29–43

    Article  PubMed  CAS  Google Scholar 

  20. Piguet P-F. Cytokines involved in pulmonary fibrosis. Int Rev Exp Pathol 34B:173–181

    Google Scholar 

  21. Piguet PF, Collart MA, Grau. GF, Kapanci Y, Vassalli P (1989) Tumor necrosis factor-a cachectin plays a key role in bleomycin-induced pneumopathy and fibrosis. J Exp Med 170:655–663

    Article  PubMed  CAS  Google Scholar 

  22. Rønnov-Jessen L, Petersen OW (1993) Induction of -smooth muscle actin by transforming growth factor-βl in quiescent human breast gland fibroblasts. Implications for myofibroblast generation in breast neoplasia. Implications for myofibroblast generation in breast neoplasia. Lab Invest 68:696–707

    PubMed  Google Scholar 

  23. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche NS, Wakefield LM, Heine UI, Liotta LA, Falanga V, Kehrl JH, Fauci AS (1986) Transforming growth factor type β: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A 83:4167–4171

    Article  PubMed  CAS  Google Scholar 

  24. Rubbia-Brandt L, Sappino A-P, Gabbiani G (1991) Locally applied GM-CSF induces the accumulation of smooth muscle actin containing myofibroblasts. Virchows Arch B Cell Pathol 60:73–82

    Article  CAS  Google Scholar 

  25. Sappino AP, Schürch W, Gabbiani G (1990) Differentiation repertoire of fibroblastic cells: expression of cytoskeletal proteins as marker of phenotypic modulations. Lab Invest 63: 144–161

    PubMed  CAS  Google Scholar 

  26. Sato Y, Rifkin DB (1989) Inhibition of endothelial cell movement by pericytes and smooth muscle cells: activation of a latent transforming growth factor-β - like molecule by plasmin during co-culture. J Cell Biol 109:309–315

    Article  PubMed  CAS  Google Scholar 

  27. Schmitt-Graff A, Desmouliere A, Gabbiani G (1994) Heterogeneity of myofibroblast phenotypic features: an example of fibroblastic cell plasticity. Virchows Arch 425:3–24

    Article  PubMed  CAS  Google Scholar 

  28. Schürch W, Seemayer TA, Gabbiani G (1992) Myofibroblast. In: Sternberg SS (ed) Histology for pathologists. Raven Press, New York, pp 109–144

    Google Scholar 

  29. Sime PJ, Xing Z, Graham FL, Csaky KG, Gauldie J (1997) Adenovector-mediated gene transfer of active TGF-β1 induces prolonged severe fibrosis in rat lung. J Clin Invest 100:768–776

    Article  PubMed  CAS  Google Scholar 

  30. Sime PJ, Marr RA, Gauldie D, Xing Z, Hewlett BR, Graham FL, Gauldie J (1998) Transfer of TNFa to rat lung induces severe pulmonary inflammation and patchy interstitial fibrogenesis with induction of TGF-β1 and myofibroblasts.

    Google Scholar 

  31. Tremblay GM, Jordana M, Gauldie J, Särnstrand B (1995) Fibroblasts as effector cells in fibrosis. In: Phan SH, Thrall RS (eds) Pulmonary fibrosis. Marcel Dekker Inc, New York, pp 541–577

    Google Scholar 

  32. Ulich TR (1993) Tumor necrosis factor. In: Kelley J (ed) Cytokines of the lung. Marcel Dekker, New York, pp 307–332

    Google Scholar 

  33. Vyalov S, Desmoulière A, Gabbiani G (1993) GM-CSF-induced granulation tissue formation: relationships between macrophage and myofibroblast accumulation. Virchows Arch B Cell Pathol 63:231–239

    Article  CAS  Google Scholar 

  34. Xing Z, Braciak T, Ohkawara Y, Sallenave J-M, Roley R, Sime PJ, Jordana M, Graham FL, Gauldie J (1996) Gene transfer for cytokine functional studies in the lung: the multifunctional role of GM-CSF in pulmonary inflammation. J Leukocyte Biol 59:481–488

    PubMed  CAS  Google Scholar 

  35. Xing Z, Ohkawara Y, Jordana M, Graham FL, Gauldie J (1996) Transfer of granulocyte-macrophage colony-stimulating factor gene to rat lung induces eosinophilia, monocytosis, and fibrotic reactions. J Clin Invest 97:1102–1110

    Article  PubMed  CAS  Google Scholar 

  36. Xing Z, Tremblay GM, Sime PJ, Gauldie J (1997) Overexpression of granulocyte-macrophage colony-stimulating factor induces pulmonary granulation tissue formation and fibrosis by induction of transforming growth factor-β1 and myofibroblast accumulation. Am J Pathol 150:59–66

    PubMed  CAS  Google Scholar 

  37. Xing Z, Braciak T, Jordana M, Croitoru K, Graham FL, Gauldie J (1994) Adenovirus-mediated cytokine gene transfer at tissue sites. Overexpression of IL-6 induces lymphocytic hyperplasia in the lung. J Immunol 153:4059–4069

    PubMed  CAS  Google Scholar 

  38. Zhan K, Rekhter MD, Gordon D, Phan SH (1994) Myofibroblasts and their role in lung collagen gene expression during pulmonary fibrosis. A combined immunohistochemical and in situ hybridization study. Am J Pathol 145:114–125

    Google Scholar 

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Authors
  1. J. Gauldie
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  2. P. J. Sime
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  3. Z. Xing
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  4. B. Marr
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  5. G. M. Tremblay
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Editor information

Editors and Affiliations

  1. GREF, Université Victor Segalen Bordeaux 2, 146, Rue Léo-Saignat, 33076, Bordeaux Cedex, France

    Alexis Desmoulière

  2. Départment de Nutrition, Université de Montréal, Pavillon Liliane-de-Stewart C. P. 6128, Succursale Centre-Ville, Montréal, Québec, H3C 3J7, Canada

    Beatriz Tuchweber

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© 1999 Springer-Verlag Berlin Heidelberg

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Gauldie, J., Sime, P.J., Xing, Z., Marr, B., Tremblay, G.M. (1999). Transforming Growth Factor-β Gene Transfer to the Lung Induces Myofibroblast Presence and Pulmonary Fibrosis. In: Desmoulière, A., Tuchweber, B. (eds) Tissue Repair and Fibrosis. Current Topics in Pathology, vol 93. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-58456-5_5

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  • DOI: https://doi.org/10.1007/978-3-642-58456-5_5

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-63603-5

  • Online ISBN: 978-3-642-58456-5

  • eBook Packages: Springer Book Archive

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