TGF beta and TGF alpha, antagonistic effect in vitro on extracellular matrix accumulation by chick skin fibroblasts at two distinct embryonic stages

ECM macromolecules create a specific environ ment that participates in the control of cell proliferation and differentiation during embryogenesis. Qua ntitative and qualitative alterations in the ECM may depend on several grow th factors that modify cell metabolism. Since transforming growth factor be ta (TGF beta) and alpha (TGF alpha) are abundantly expressed during embryon ic development in organs in which epithelial-mesenchymal interactions occur , the aim of this study was to determine: a) the effect of TGF beta on the phenotype of 7 and 14 day chick embryo back skin (CEBS) fibroblasts by eval uating the neosynthesis of GAG, collagen and fibronectin; b) whether TGF al pha and TGF beta production, in particular TGF beta(3) and TGF beta(4), and the number of TGF beta receptors change during these two stages of embryon ic development. The results show that the neosynthesis of ECM macromolecule s, tested using radiolabelled precursors, is increased by TGF beta. The gro wth factor generally favours cellular accumulation more than secretion. As far as GAG is concerned, TGF beta has a greater stimulatory effect on sulph ated GAG than on HA. Specific bioassay shows that TGF beta(3) and TGF beta( 4) activity is higher in 7 day than 14 day CEBS fibroblasts. Moreover, TGF beta(3) and TGF beta(4) mRNA expression is increased in the first stages of development. Instead, the level of TGF alpha increases in successive devel opmental stages. Since TGF alpha stimulates the synthesis and secretion of HA, and HA binds and inactivates TGF beta, the greater quantity of HA in 14 day fibroblasts may contribute to reducing the TGF beta effect. Overall ou r data suggest that the production of TGF beta and TGF alpha are age-depend ent and that the balance between the two growth factors may be a mechanism for controlling skin differentiation.