TGF-β decreases type I collagen and scarring after labioplasty

Cleft lip is a common congenital malformation, and labioplasty performed on infants to repair such defects often results in severe scar formation. Since TGF-beta3 has been implicated in wound healing, we therefore hypothesized that TGF-beta3 functions to reduce scarring after cleft lip repair. In this investigation, we demonstrated that exogenous TGF-beta3 reduced scar formation in an incised and sutured mouse lip in vivo. During labioplasty, endogenous TGF-beta3 expression was also elevated. In vitro experiments showed that exogenous TGF-beta3 reduced type I collagen accumulation. Furthermore, TGF-beta3 inhibited alpha-smooth-muscle actin expression, a marker for myofibroblasts. In tandem, TGF-beta3 induced the expression and activity of MMP-9. Analysis of our data suggests that TGF-beta3 is normally secreted following labioplastic wound healing. An elevated level of TGF-beta3 reduces type I collagen deposition by restricting myofibroblast differentiation and thereby collagen synthesis, and by promoting collagen degradation by MMP-9. In combination, these events lead to TGF-beta3-mediated reduced scar formation.