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Giulio Gabbiani and the discovery of myofibroblasts

  • History of Inflammation
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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.

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References

  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.

    Article  CAS  PubMed  Google Scholar 

  2. Gabbiani G, Hinz B. Cell-matrix and cell-cell contacts of myofibroblasts: role in connective tissue remodeling. Thromb Haemost. 2003;90:993–1002.

    Article  CAS  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  6. Gabbiani G. Cytoplasmic filaments and gap junctions in epithelial cells and myofibroblasts during wound healing. J Cell Biol. 1978;76:561–8.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  17. Kis K, Liu X, Hagood JS. Myofibroblast differentiation and survival in fibrotic disease. Expert Rev Mol Med 2011; 13:e27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  20. Friedman SL. Evolving challenges in hepatic fibrosis. Nat Rev Gastroenterol Hepatol. 2010;7:425–36.

    Article  PubMed  Google Scholar 

  21. Desmoulière A. Hepatic stellate cells: the only cells involved in liver fibrogenesis? A dogma challenged. Gastroenterology. 2007;132:2059–62.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  26. Mareel M, Oliveira MJ, Madani I. Cancer invasion and metastasis: interacting ecosystems. Virchows Arch. 2009;454:599–622.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  28. Hinz B, Gabbiani G. Fibrosis: recent advances in myofibroblast biology and new therapeutic perspectives. F1000 Biol Rep. 2010;2:78.

    Article  PubMed  PubMed Central  Google Scholar 

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Authors and Affiliations

  1. Department of Basic Medical Sciences, Neurosciences and Sensory Organs, University of Bari Medical School, Policlinico-Piazza G. Cesare, 11, 70124, Bari, Italy

    Domenico Ribatti & Roberto Tamma

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  1. Domenico Ribatti
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  2. Roberto Tamma
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Correspondence to Domenico Ribatti.

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Ribatti, D., Tamma, R. Giulio Gabbiani and the discovery of myofibroblasts. Inflamm. Res. 68, 241–245 (2019). https://doi.org/10.1007/s00011-018-01211-x

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  • DOI: https://doi.org/10.1007/s00011-018-01211-x

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