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

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.