Contractility, transforming growth factor-beta, and plasmin in fetal skin fibroblasts: role in scarless wound healing.
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.
Coleman
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Division of Pediatric Surgery, Childrens Hospital Los Angeles Research Institute, California 90027, USA.
Tuan
T L
TL
Buckley
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Anderson
K D
KD
Warburton
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D
D000818:Animals; D002478:Cells, Cultured; D002921:Cicatrix / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D003094:Collagen; D017077:Culture Media, Conditioned; D005260:Female; D005333:Fetus / Q000166:cytology / Q000378:metabolism*; D005341:Fibrinolysin / Q000096:biosynthesis*; D005347:Fibroblasts / Q000378:metabolism; D005782:Gels; D005865:Gestational Age; D051379:Mice; D011247:Pregnancy; D049188:Prenatal Injuries; D012867:Skin / Q000166:cytology / Q000293:injuries* / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D014945:Wound Healing / Q000502:physiology*
D017077:Culture Media, Conditioned; D005782:Gels; D016212:Transforming Growth Factor beta; D003094:Collagen; D005341:Fibrinolysin