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

G Serini, ML Bochaton-Piallat, P Ropraz… - The Journal of cell …, 1998 - rupress.org
G Serini, ML Bochaton-Piallat, P Ropraz, A Geinoz, L Borsi, L Zardi, G Gabbiani
The Journal of cell biology, 1998rupress.org
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 …
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.
rupress.org