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Inflammation Research

, Volume 68, Issue 3, pp 241–245 | Cite as

Giulio Gabbiani and the discovery of myofibroblasts

  • Domenico RibattiEmail author
  • Roberto Tamma
History of Inflammation
  • 70 Downloads

Abstract

Myofibroblasts, specialized fibroblasts expressing the protein alpha-smooth muscle actin, are instrumental in wound contraction during normal wound healing. Tissue shortening is then stabilized by the synthesis of extracellular matrix, collagen in particular. Alpha-smooth muscle actin within myofibroblasts becomes organized in filamentous bundles, called stress fibers, that allow the retractile movement producing wound contraction. During hypertrophic scarring, skin deformations depend on the inappropriate action of these stress fibers that for unknown reasons persist even after the epithelialization of the wound. This historical review article is dedicated to the reconstruction of the discovery of this cell by the Italian scientist Giulio Gabbiani.

Keywords

Inflammation History of medicine Myofibroblasts Wound healing 

Notes

References

  1. 1.
    Gabbiani G, Ryan GB, Majno G. Presence of modified fibroblasts in granulation tissue and their possible role in wound contraction. Experientia. 1971;27:549–50.CrossRefGoogle Scholar
  2. 2.
    Gabbiani G, Hinz B. Cell-matrix and cell-cell contacts of myofibroblasts: role in connective tissue remodeling. Thromb Haemost. 2003;90:993–1002.CrossRefGoogle Scholar
  3. 3.
    Desmouliere A, Redard M, Darby I, Gabbiani G. Apoptosis mediates the decrease in cellularity during the transition between granulation tissue and scar. Am J Pathol. 1995;146:56–66.Google Scholar
  4. 4.
    Desmoulière A, Badid C, Bochaton-Piallat M-L, Gabbiani G. Apoptosis during wound healing, fibrocontractive diseases and vascular wall injury. Int J Biochem Cell Biol. 1997;29:19–30.CrossRefGoogle Scholar
  5. 5.
    Dugina V, Fontao L, Chaponnier C, Vasiliev J, Gabbiani G. Focal adhesion features during myofibroblastic differentiation are controlled by intracellular and extracellular factors. J Cell Sci. 2001;114:3285–96.Google Scholar
  6. 6.
    Gabbiani G. Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing. J Cell Biol. 1978;76:561–8.CrossRefGoogle Scholar
  7. 7.
    Skalli O. A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol. 1986;103:2787–96.CrossRefGoogle Scholar
  8. 8.
    Hinz B, Celetta G, Tomasek JJ, Gabbiani G, Chaponnier C. Alpha-smooth muscle actin expression upregulates fibroblast contractile activity. Mol Biol Cell. 2001;12:2730–41.CrossRefGoogle Scholar
  9. 9.
    Tomasek JJ, Gabbiani G, Hinz B, Chaponnier C, Brown RA. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol. 2002;3:349–63.CrossRefGoogle Scholar
  10. 10.
    Konttinen YT, Saari H, Santavirta S, Antti-Poika I, Sorsa T, Nykänen P, et al. Synovial fibroblasts. Scand J Rheumatol. 1988;17:95–103.CrossRefGoogle Scholar
  11. 11.
    Janin A, Konttinen YT, Gronblad M, Karhunen P, Gosset D, Malmstrom M. Fibroblast markers in labial salivary gland biopsies in progressive systemic sclerosis. Clin Exp Rheumatol. 1990;8:237–42.Google Scholar
  12. 12.
    Rønnov-Jessen L, Petersen OW, Koteliansky VE, Bissell MJ. The origin of the myofibroblasts in breast cancer. Recapitulation of tumor environment in culture unravels diversity and implicates converted fibroblasts and recruited smooth muscle cells. J Clin Investig. 1995;95:859–73.CrossRefGoogle Scholar
  13. 13.
    Desmouliere A, Rubbia-Brandt L, Grau G, Gabbiani G. Heparin induces alpha-smooth muscle actin expression in cultured fibroblasts and in granulation tissue myofibroblasts. Lab Invest. 1992;67:716–26.Google Scholar
  14. 14.
    Desmouliere A. Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol. 1993;122:103–11.CrossRefGoogle Scholar
  15. 15.
    Serini G, Bochaton-Piallat M-L, Ropraz P, Geinoz A, Borsi L, Zardi L, et al. The fibronectin domain ED-A Is crucial for myofibroblastic phenotype induction by transforming growth factor-β1. J Cell Biol. 1998;142:873–81.CrossRefGoogle Scholar
  16. 16.
    Vaughan MB, Howard EW, Tomasek JJ. Transforming growth factor-β1 promotes the morphological and functional differentiation of the myofibroblast. Exp Cell Res. 2000;257:180–9.CrossRefGoogle Scholar
  17. 17.
    Kis K, Liu X, Hagood JS. Myofibroblast differentiation and survival in fibrotic disease. Expert Rev Mol Med 2011; 13:e27.CrossRefGoogle Scholar
  18. 18.
    Rajkumar VS, Howell K, Csiszar K, Denton CP, Black CM, Abraham DJ. Shared expression of phenotypic markers in systemic sclerosis indicate a convergence of pericytes and fibroblasts to a myofibroblast lineage in fibrosis. Arthr Res Ther. 2005;7:R1113.CrossRefGoogle Scholar
  19. 19.
    Aden N, Nuttall A, Shiwen X, de Winter P, Leask A, Black CM, et al. Epithelial cells promote fibroblast activation via IL-1α in systemic sclerosis. J Investig Dermatol. 2010;130:2191–200.CrossRefGoogle Scholar
  20. 20.
    Friedman SL. Evolving challenges in hepatic fibrosis. Nat Rev Gastroenterol Hepatol. 2010;7:425–36.CrossRefGoogle Scholar
  21. 21.
    Desmoulière A. Hepatic stellate cells: the only cells involved in liver fibrogenesis? A dogma challenged. Gastroenterology. 2007;132:2059–62.CrossRefGoogle Scholar
  22. 22.
    Desmouliere A, Guyot C, Gabbiani G. The stroma reaction myofibroblast: a key player in the control of tumor cell behavior. Int J Dev Biol. 2004;48:509–17.CrossRefGoogle Scholar
  23. 23.
    Iwano M, Plieth D, Danoff TM, Xue C, Okada H, Neilson EG. Evidence that fibroblasts derive from epithelium during tissue fibrosis. J Clin Investig. 2002;110:341–50.CrossRefGoogle Scholar
  24. 24.
    Peterson D. Expression of Gi-2α and Gsα in myofibroblasts localized to the infarct scar in heart failure due to myocardial infarction. Cardiovasc Res. 1999;41:575–85.CrossRefGoogle Scholar
  25. 25.
    Squires CE, Escobar GP, Payne JF, Leonardi RA, Goshorn DK, Sheats NJ, et al. Altered fibroblast function following myocardial infarction. J Mol Cell Cardiol. 2005;39:699–707.CrossRefGoogle Scholar
  26. 26.
    Mareel M, Oliveira MJ, Madani I. Cancer invasion and metastasis: interacting ecosystems. Virchows Arch. 2009;454:599–622.CrossRefGoogle Scholar
  27. 27.
    Darby IA, Zakuan N, Billet F, Desmoulière A. The myofibroblast, a key cell in normal and pathological tissue repair. Cell Mol Life Sci. 2015;73:1145–57.CrossRefGoogle Scholar
  28. 28.
    Hinz B, Gabbiani G. Fibrosis: recent advances in myofibroblast biology and new therapeutic perspectives. F1000 Biol Rep. 2010;2:78.CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Basic Medical Sciences, Neurosciences and Sensory OrgansUniversity of Bari Medical SchoolBariItaly

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