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

Ann Surg. 1995 Aug;222(2):146-54. doi: 10.1097/00000658-199508000-00006.

Abstract

Objective: Fetal skin wounds heal without scarring. To determine the role of TGF-beta 1 in fetal wound healing, mRNA expression of TGF-beta 1 was analyzed in human fetal and adult skin wounds.

Methods: Human fetal 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-beta 1 mRNA expression and species-specific immunohistochemistry for fibroblasts, macrophages, and neutrophils were performed in human adult wounds, fetal wounds, and fetal wounds treated with a TGF-beta 1 slow release disk.

Results: Transforming growth factor-beta 1 mRNA expression was induced by wounding adult skin. No TGF-beta 1 mRNA upregulation was detected in human fetal skin after wounding. However, when exogenous TGF-beta 1 was added to human fetal skin, induction of TGF-beta 1 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-beta 1 is an important modulator in scar formation. Anti-TGF-beta 1 strategies may promote scarless healing in adult wounds.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aging
  • Animals
  • Cicatrix / etiology*
  • Cicatrix / physiopathology
  • Disease Models, Animal
  • Female
  • Fetus / drug effects*
  • Fetus / physiology
  • Fibroblasts / physiology
  • Gene Expression Regulation
  • Humans
  • Macrophages / physiology
  • Mice
  • Mice, Nude
  • Neutrophils / physiology
  • RNA, Messenger / genetics
  • Skin / drug effects*
  • Skin / physiopathology
  • Skin Transplantation
  • Species Specificity
  • Transforming Growth Factor beta / administration & dosage
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / pharmacology*
  • Transforming Growth Factor beta / physiology
  • Transplantation, Heterologous
  • Wound Healing / genetics

Substances

  • RNA, Messenger
  • Transforming Growth Factor beta