Since pronounced differences exist between the fetal and adult repair processes, 
we studied the proliferative response of skin fibroblasts from these two stages 
to transforming growth factor-beta (TGF-beta), a cytokine with a broad range of 
activities in tissue repair. Here, we present evidence that TGF-beta inhibits 
fetal human skin fibroblasts, while it is stimulatory for adult ones. This 
proliferative effect of TGF-beta was found to be concentration- dependent, but 
isoform-independent. Furthermore, even a transient exposure of the cells to this 
growth factor was sufficient to exert its stimulatory or inhibitory action. 
Accordingly, we have studied the immediate responses provoked by TGF-beta in 
major signaling pathways, and we have found that it induces a rapid activation 
of the SMAD pathway, i.e., phosphorylation and nuclear translocation of SMAD2, 
followed by dephosphorylation, most probably due to degradation by the 
proteasome. However, similar intensity and kinetics of this activation have been 
observed in both fetal and adult fibroblasts. On the other hand, curcumin, a 
natural product with wound healing properties that inhibits several 
intracellular signaling pathways, was found to completely abrogate the 
inhibitory effect of TGF-beta1 on human fetal skin fibroblasts, without 
affecting the stimulatory action on fibroblasts from adult donors. In 
conclusion, there is a major radical in the proliferative response of fetal and 
adult human skin fibroblasts to TGF-beta, possibly reflecting the different 
repair strategies followed in these two stages of development.