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-beta1) induces scarring in fetal skin by altering proteinase synthesis. A model of human fetal skin 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-beta1 induces scarring. Proteinases were detected by immunohistochemistry in untransplanted fetal skin, untransplanted adult skin, TGF-beta1-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-beta1 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-beta1 is accompanied by a decrease in interstitial collagenase. These data suggest that the increased matrix metalloproteinases found in fetal skin contribute to scarless healing and that the fibrotic effects of TGF-beta1 on fetal skin may be mediated in part by decreasing the synthesis of interstitial collagenase.
Bullard
K M
KM
Department of Surgery (Division of Pediatric Surgery), the Fetal Treatment Center, University of California, San Francisco, 94143-0570, USA.
Cass
D L
DL
Banda
M J
MJ
Adzick
N S
NS
D000328:Adult; D000704:Analysis of Variance; D000818:Animals; D002921:Cicatrix / Q000503:physiopathology; D017364:Collagenases / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D012867:Skin / Q000196:embryology*; D016038:Skin Transplantation; D016212:Transforming Growth Factor beta / Q000502:physiology*; D014945:Wound Healing / Q000502:physiology*
D016212:Transforming Growth Factor beta; D017364:Collagenases