Transforming growth factor‐β 3 affects plasminogen activator inhibitor‐1 expression in fetal mice and modulates fibroblast‐mediated collagen gel contraction

For over two decades, the precise role of transforming growth factor‐β (TGF‐β) isoforms in scarless healing of mammalian fetal skin wounds has generated much interest. Although their exact role remains to be established, it has been suggested that high TGF‐β3 activity may correlate with a scarless phenotype. Previously, we showed that plasminogen activator inhibitor‐1 (PAI‐1), a known TGF‐β downstream molecule and marker of fibrosis, is also developmentally regulated during fetal skin development. In this study, the relationship between TGF‐β3 and PAI‐1 was investigated using embryonic day 14.5 TGF‐β3 knockout (ko) mice. The results showed increased PAI‐1 expression in the epidermis and dermis of ko mice, using an ex vivo limb‐wounding study. Furthermore, increased PAI‐1 expression and activity was seen in embryo extracts and conditioned media of ko dermal fibroblasts. When TGF‐β3 knockout fibroblasts were placed into three‐dimensional collagen matrices, they were found to have decreased collagen gel contraction, suggesting altered cell–matrix interaction. These findings provide a further avenue for the interactive role of TGF‐β3 and PAI‐1 during fetal scarless repair.