TGF-beta 3 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-beta 3 has been implicated in wound healing, we therefore hypothesized that TGF-beta 3 functions to reduce scarring after cleft lip repair. In this investigation, we demonstrated that exogenous TGF-beta 3 reduced scar formation in an incised and sutured mouse lip in vivo. During labioplasty, endogenous TGF-beta 3 expression was also elevated. In vitro experiments showed that exogenous TGF-beta 3 reduced type I collagen accumulation. Furthermore, TGF-beta 3 inhibited alpha-smooth-muscle actin expression, a marker for myofibroblasts. In tandem, TGF-beta 3 induced the expression and activity of MMP-9. Analysis of our data suggests that TGF-beta 3 is normally secreted following labioplastic wound healing. An elevated level of TGF-beta 3 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-beta 3-mediated reduced scar formation.
Hosokawa
R
R
Graduate School of Dental Science, Faculty of Dental Science, Kyushu University, Fukuoka, Japan.
Nonaka
K
K
Morifuji
M
M
Shum
L
L
Ohishi
M
M
D000199:Actins / Q000096:biosynthesis / Q000187:drug effects; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002921:Cicatrix / Q000517:prevention & control*; D002971:Cleft Lip / Q000601:surgery*; D024042:Collagen Type I / Q000096:biosynthesis* / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects; D008046:Lip / Q000601:surgery*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D051379:Mice; D008817:Mice, Mutant Strains; D019647:Oral Surgical Procedures / Q000379:methods*; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology; D053782:Transforming Growth Factor beta3
D000199:Actins; D024042:Collagen Type I; D011994:Recombinant Proteins; C509045:Tgfb3 protein, mouse; D016212:Transforming Growth Factor beta; D053782:Transforming Growth Factor beta3; D020780:Matrix Metalloproteinase 9