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-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.
Lin
R Y
RY
Department of Surgery, University of California-San Francisco, USA.
Sullivan
K M
KM
Argenta
P A
PA
Meuli
M
M
Lorenz
H P
HP
Adzick
N S
NS
D000328:Adult; D000375:Aging; D000818:Animals; D002921:Cicatrix / Q000209:etiology* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008819:Mice, Nude; D009504:Neutrophils / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D012867:Skin / Q000187:drug effects* / Q000503:physiopathology; D016038:Skin Transplantation; D013045:Species Specificity; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D014183:Transplantation, Heterologous; D014945:Wound Healing / Q000235:genetics
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta