Contractility, transforming growth factor-beta, and plasmin in fetal skin fibroblasts: role in scarless wound healing

Abstract

The early fetus responds to cutaneous wounds in a fundamentally different way from the adult; fetal wounds heal without scars. Wound contraction is a vital component of wound healing. The cytokine transforming growth factor (TGF)-beta promotes wound contraction and can be activated by the serine protease plasmin. Herein, we explored whether murine skin fibroblast contractile properties, TGF-beta, and plasmin formation are developmentally regulated. Our results showed that early fetal mouse embryonic day 15 skin fibroblasts contracted a collagen gel less, secreted less active and total TGF-beta, and generated less plasmin than either late fetal (embryonic day 17) or adult skin fibroblasts. Furthermore, there was a slight positive correlation between the formation of plasmin and the level of activation of TGF-beta. We conclude that early fetal mouse skin fibroblasts contract a collagen gel and secrete and activate TGF-beta to a lesser extent than do late fetal and adult skin fibroblasts. We speculate that the fetal skin fibroblast undergoes a developmental transition that causes wounds in mouse to contract at or after embryonic day 17. Further, this developmental transition is influenced by growth factor-fibroblast interactions and coincides with the emergence of the skin fibroblast's ability to generate plasmin and activate TGF-beta.