Exogenous transforming growth factor beta(2) modulates collagen I and collagen III synthesis in proliferative scar xenografts in nude rats.
BACKGROUND
Keloid and hypertrophic scars are fibrous dermal tumors characterized by overabundant collagen deposition. Previous studies demonstrated that exogenous transforming growth factor beta (TGF-beta) might increase collagen production in incisional wound models and in vitro. Using an in vivo model of human scar xenografts maintained in congenitally athymic, asplenic "nude" rats, we examined endogenous TGF-beta(2), collagen I, and collagen III levels in keloids and burn hypertrophic scars treated with TGF-beta(2) and TGF-beta(2) antibody.


METHODS
Fresh keloid and burn hypertrophic scar specimens excised from human subjects were explanted to pedicled flaps based on the superficial inferior epigastric vessels in athymic "nude" rats. These flaps were allowed to mature for 3 weeks, after which the scar explants were directly perfused with 200 ng of TGF-beta(2) or 250 microg of TGF-beta(2) antibody daily for 5 consecutive days, then again on Days 10, 15, and 20. Biopsies were taken 30 and 120 days following the initiation of treatment. Immunohistochemical staining was then performed for TGF-beta(2), collagen I, and collagen III. The intensity of staining was quantified.


RESULTS
Our results demonstrated that treatment of human proliferative scars with exogenous TGF-beta(2) results in a significant increase in endogenous TGF-beta(2), collagen I, and collagen III production. By contrast, exogenous addition of anti-TGF-beta(2) antibody significantly decreased endogenous TGF-beta(2), collagen I, and collagen III production.


CONCLUSIONS
This study supports a causative role for TGF-beta(2) in the formation of proliferative scars and suggests that TGF-beta(2) antibody may be a new potential antiscarring agent.
Wang
X
X
Repair and Rehabilitation, The Institute of Tissue Regeneration, Bay Pines, Florida 33744, USA.
Smith
P
P
Pu
L L
LL
Kim
Y J
YJ
Ko
F
F
Robson
M C
MC
D000818:Animals; D002056:Burns / Q000628:therapy; D002455:Cell Division; D002921:Cicatrix / Q000209:etiology* / Q000473:pathology / Q000628:therapy; D003094:Collagen / Q000096:biosynthesis*; D006801:Humans; D051381:Rats; D011923:Rats, Nude; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000494:pharmacology* / Q000502:physiology; D014183:Transplantation, Heterologous
D016212:Transforming Growth Factor beta; D003094:Collagen