Cleft lip is a common congenital malformation, and labioplasty performed on infants to repair such defects often results in severe scar formation. Since TGF-β3 has been implicated in wound healing, we therefore hypothesized that TGF-β3 functions to reduce scarring after cleft lip repair. In this investigation, we demonstrated that exogenous TGF-β3 reduced scar formation in an incised and sutured mouse lip in vivo. During labioplasty, endogenous TGF-β3 expression was also elevated. In vitro experiments showed that exogenous TGF-β3 reduced type I collagen accumulation. Furthermore, TGF-β3 inhibited alpha-smooth-muscle actin expression, a marker for myofibroblasts. In tandem, TGF-β3 induced the expression and activity of MMP-9. Analysis of our data suggests that TGF-β3 is normally secreted following labioplastic wound healing. An elevated level of TGF-β3 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-β3-mediated reduced scar formation.
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