Transforming growth factor beta-1 decreases interstitial collagenase in healing human fetal skin

Fetal dermal wounds heal without scarring. Because wound repair requires extracellular matrix turnover, the authors hypothesized that fetal skin would have increased levels of proteinases responsible for matrix degradation compared with adult skin. It was further hypothesized that transforming growth factor beta-1 (TGF-beta 1) induces scarring in fetal skin by altering proteinase synthesis. A model of human fetal shin transplanted subcutaneously onto immunodeficient mice was used to study the role of matrix metalloproteinases in healing human fetal skin. In this model, transplanted second trimester fetal skin heals without scarring; addition of TGF-beta 1 induces scarring. Proteinases were detected by immunohistochemistry in untransplanted fetal shin, untransplanted adult skin, TGF-beta 1-treated fetal skin grafts, and sucrose-treated control grafts. In untransplanted fetal skin, interstitial collagenase, stromelysin-1, and gelatinase A were found in dermal cells and keratinocytes, and around vascular structures. Proteinases were detected in adult skin at similar locations but stained less intensely. Addition of TGF-beta 1 decreased interstitial collagenase in fetal skin, but detection of gelatinase A and stromelysin-1 was unchanged. The authors conclude that matrix metalloproteinases are present in midgestation human fetal skin and that more proteinase-containing cells are found in fetal skin than in adult skin. Manipulation of fetal skin with TGF-beta 1 is accompanied by a decrease in interstitial collagenase. These data suggest that the increased matrix metalloproteinases found in fetal shin contribute to scarless healing and that the fibrotic effects of TGF-beta 1 on fetal skin may be mediated in part by decreasing the synthesis of interstitial collagenase. Copyright (C) 1997 by W.B. Saunders Company.