Exogenous transforming growth factor-beta amplifies its own expression and induces scar formation in a model of human fetal skin repair

Richard Y. Lin, Kerry M. Sullivan, Peter A. Argenta, Martin Meuli, H. Peter Lorenz, N. Scott Adzick

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Objective: Fetal skin wounds heal without scarring. To determine the role of TGF-β1 in fetal wound healing, mRNA expression of TGF-β1 was analyzed in human total and adult skin wounds. Methods: Human total skin transplanted to a subcutaneous location on an adult athymic mouse that was subsequently wounded heals without scar, whereas human adult skin heals with scar formation in that location. In situ hybridization for TGF-β1 mRNA expression and species-specific immunohistochemistry for fibroblasts, macrophages, and neutrophils were performed in human adult wounds, total wounds, and total wounds treated with a TGF-β1 slow release disk. Results: Transforming growth factor-β1 mRNA expression was induced by wounding adult skin. No TGF-β1 mRNA upregulation was detected in human total skin after wounding. However, when exogenous TGF-β1 was added to human fetal skin, induction of TGF-β1 mRNA expression in human fetal fibroblasts occurred, an adult-like inflammatory response was detected, and the skin healed with scar formation. Conclusions: Transforming growth factor-β1 is an important modulator in scar formation. Anti-TGF-β1 strategies may promote scarless healing in adult wounds.

Original languageEnglish (US)
Pages (from-to)146-154
Number of pages9
JournalAnnals of surgery
Volume222
Issue number2
DOIs
StatePublished - Aug 1995

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