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)-β promotes wound contraction and can be activated by the serine protease plasmin. Herein, we explored whether murine skin fibroblast contractile properties, TGF-β, 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-β, 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-β. We conclude that early fetal mouse skin fibroblasts contract a collagen gel and secrete and activate TGF-β 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-β.
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Abbreviations
- TGF-β:
-
transforming growth factor-β
- DMEM:
-
Dulbecco's modified Eagle's medium
- PAI:
-
plasminogen activator inhibitor
- PA:
-
plasminogen activator
- PDGF:
-
platelet-derived growth factor
- E15, E17:
-
embryonic day 15, 17
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Acknowledgements
The authors thank Judy Zhu for excellent technical assistance, Earl Leonard for assistance in the statistical analysis of the data, and Dr. Daniel Rifkin of New York University of for the generous gift of PAI-1-transfected mink lung epithelial cells.
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Supported by a Childrens Hospital Los Angeles Research Institute Career Development Award (to C.L.C.) and by National Institutes of Health Grants HL44060 and HL4977 (to D. W.) and AR40409 (to T.-L.T.).
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Coleman, C., Tuan, TL., Buckley, S. et al. Contractility, Transforming Growth Factor-β, and Plasmin in Fetal Skin Fibroblasts: Role in Scarless Wound Healing. Pediatr Res 43, 403–409 (1998). https://doi.org/10.1203/00006450-199803000-00016
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DOI: https://doi.org/10.1203/00006450-199803000-00016
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