TGFbeta and TGFalpha, antagonistic effect in vitro on extracelluar matrix accumulation by chick skin fibroblasts at two distinct embryonic stages.

DECM macromolecules create a specific environment that participates in the control of cell proliferation and differentiation during embryogenesis. Quantitative and qualitative alterations in the ECM may depend on several growth factors that modify cell metabolism. Since transforming growth factor b (TGFb) and a (TGFa) are abundantly expressed during embryonic development in organs in which epithelial-mesenchymal interactions occur, the aim of this study was to determine: a) the effect of TGFb on the phenotype of 7 and 14 day chick embryo back skin (CEBS) fibroblasts by evaluating the neosynthesis of GAG, collagen and fibronectin; b) whether TGFa and TGFb production, in particular TGFb3 and TGFb4, and the number of TGFb receptors change during these two stages of embryonic development. The results show that the neosynthesis of ECM macromolecules, tested using radiolabelled precursors, is increased by TGFb. The growth factor generally favours cellular accumulation more than secretion. As far as GAG is concerned, TGFb has a greater stimulatory effect on sulphated GAG than on HA. Specific bioassay shows that TGFb3 and TGFb4 activity is higher in 7 day than 14 day CEBS fibroblasts. Moreover, TGFb3 and TGFb4 mRNA expression is increased in the first stages of development. Instead, the level of TGFa increases in successive developmental stages. Since TGFa stimulates the synthesis and secretion of HA, and HA binds and inactivates TGFb, the greater quantity of HA in 14 day fibroblasts may contribute to reducing the TGFb effect. Overall our data suggest that the production of TGFb and TGFa are agedependent and that the balance between the two growth factors may be a mechanism for controlling skin differentiation.