A role for TGF-beta1-induced cellular responses during wound healing of the non-scarring early human fetus?

Early human fetuses regenerate cutaneous wounds perfectly without scarring. However, transforming growth factor-beta1 (TGF-beta1), the cytokine linked with scarring in mature tissue, is also present during fetal wound repair, albeit transiently. We present a comparison of response to TGF-beta1 by fibroblasts derived from early human fetal skin (non-scarring) and their mature (scarring) postnatal counterparts, which revealed that although fetal fibroblasts do indeed differentiate into myofibroblasts, this response is altogether more rapid and short-lived. Fetal fibroblasts also failed to exhibit the TGF-beta1-induced increase in collagen (mRNA and protein) demonstrated by their postnatal counterparts. Fetal cells exhibited a comparatively short-lived or rapid phosphorylation of several components of the TGF-beta1 signaling pathways: Smad2/3 and c-Jun N-terminal kinase. Unlike quiescent postnatal fibroblasts, quiescent fetal fibroblasts also phosphorylated extracellular signal-regulated kinases in response to TGF-beta1. These altered responses to TGF-beta1 may well contribute to the transition between perfect regeneration and scar formation seen during development.