Differential gene expression in response to transforming growth factor-β1 by fetal and postnatal dermal fibroblasts

The multipotent growth factor transforming growth factor (TGF)-beta 1 is consistently linked with fibrosis and scarring. The perfect (scarless) healing of cutaneous wounds in early gestational age fetuses is proposed to be due to this tissue's predominance of the TGF-beta 3 isoform over the profibrotic TGF-beta 1 and 2. Nevertheless, TGF-beta 1 is present during wound healing in the early fetus and recently we demonstrated that relevant intracellular signaling pathways are activated (albeit transiently) on TGF-beta 1stimulation. This study aimed to determine whether TGF-beta 1 has different effects on gene transcription in human fetal (< 14 weeks) vs. human postnatal dermal fibroblasts, using real-time polymerase chain reaction. The regulation pattern of a number of TGF-beta response genes differed dramatically between the two cell sources. The typical autocrine loop of TGF-beta 1 autoinduction did not occur in fetal fibroblasts and genes that are normally up-regulated, connective tissue growth factor and collagen type I were actually down-regulated. Furthermore, other response genes responded in a delayed fashion (TGF-beta 3) compared with that seen in the more developmentally mature postnatal fibroblasts. Finally, genes unaltered by TGF-beta stimulation in postnatal cells, TGF-beta 2 and collagen III, were up-regulated in fetal cells. These developmentally related differences in fibroblast response to TGF-beta 1 may influence wound-healing outcome, i.e., perfect regeneration or fibrosis.