The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-β1

Guido Serini, Marie Luce Bochaton-Piallat, Patricia Ropraz, Antoine Geinoz, Laura Borsi, Luciano Zardi, Giulio Gabbiani

Research output: Contribution to journalArticlepeer-review


Transforming growth factor-β1 (TGFβ1), a major promoter of myofibroblast differentiation, induces α-smooth muscle (sn) actin, modulates the expression of adhesive receptors, and enhances the synthesis of extracellular matrix (ECM) molecules including ED-A fibronectin (FN), an isoform de novo expressed during wound healing and fibrotic changes. We report here that ED-A FN deposition precedes α-SM actin expression by fibroblasts during granulation tissue evolution in vivo and after TGFβ1 stimulation in vitro. Moreover, there is a correlation between in vitro expression of α-SM actin and ED-A FN in different fibroblastic populations. Seeding fibroblasts on ED-A FN does not elicit per se α-SM actin expression; however, incubation of fibroblasts with the anti-ED-A monoclonal antibody IST-9 specifically blocks the TGFβ1-triggered enhancement of α-SM actin and collagen type I, but not that of plasminogen activator inhibitor-1 mRNA. Interestingly, the same inhibiting action is exerted by the soluble recombinant domain ED-A, but neither of these inhibitory agents alter FN matrix assembly. Our findings indicate that ED-A-containing polymerized FN is necessary for the induction of the myofibroblastic phenotype by TGFβ1 and identify a hitherto unknown mechanism of cytokine-determined gene stimulation based on the generation of an ECM-derived permissive outside in signaling, under the control of the cytokine itself.

Original languageEnglish
Pages (from-to)873-881
Number of pages9
JournalJournal of Cell Biology
Issue number3
Publication statusPublished - Aug 10 1998


  • α-SM actin
  • Extracellular matrix
  • Fibroblast
  • Fibrosis
  • Wound healing

ASJC Scopus subject areas

  • Cell Biology


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