The temporal effects of anti-TGF-beta1, 2, and 3 monoclonal antibody on wound healing and hypertrophic scar formation.
BACKGROUND
A number of studies have implicated transforming growth factor (TGF)-beta1, 2, and 3 (TGF-beta) in wound healing and hypertrophic scarring. We propose that TGF-beta has a temporal effect on these processes. To test this hypothesis, we applied anti-TGF beta1, 2, and 3 monoclonal antibody topically to our dermal ulcer model in the rabbit ear.


METHODS
Rabbit ear wounds were treated intradermally with anti-TGF-beta1, 2, and 3 antibody at early, middle, and late time points. Treated and untreated control wounds were harvested at various time points and examined histologically to quantify wound healing and scar hypertrophy. Real-time polymerase chain reaction was performed to determine TGF-beta mRNA expression in the treated and control wounds.


RESULTS
The early treatment group demonstrated decreased new epithelium and granulation tissue (p < 0.05 versus controls). Scars harvested on days 28 and 40 displayed no difference in scar hypertrophy. Both the middle and late treatment groups demonstrated a significant decrease in scar hypertrophy (p < 0.05).


CONCLUSIONS
Treated wounds from the early treatment group displayed delayed wound healing, with no reduction in scar hypertrophy. Later treatment of wounds with the same antibody, beginning 7 days after wounding, resulted in a reduction in scar hypertrophy. These results support our hypothesis and clearly demonstrate that TGF-beta1, 2, and 3 have differential temporal effects during the wound-healing process, and are important for optimal wound healing in the first week after wounding; beyond 1 week, TGF-beta1, 2, and 3 play a critical role in hypertrophic scar formation.
Lu
Leonard
L
Wound Healing Research Laboratory, Division of Plastic and Reconstructive Surgery, Department of Surgery, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Saulis
Alexandrina S
AS
Liu
W Robert
WR
Roy
Nakshatra K
NK
Chao
Jerome D
JD
Ledbetter
Steven
S
Mustoe
Thomas A
TA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D017439:Cicatrix, Hypertrophic / Q000276:immunology*; D004431:Ear, External; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012883:Skin Ulcer / Q000276:immunology*; D013997:Time Factors; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000276:immunology* / Q000502:physiology; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3; D014945:Wound Healing / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053781:Transforming Growth Factor beta2; D053782:Transforming Growth Factor beta3