040 The Temporal Expression of the TGF-Beta Pathway in the Rabbit Ear Model of Hypertrophic Scarring

Abstract

Introduction: There is extensive data implicating the role of the TGF-beta pathway in hypertrophic scarring. However, few studies have examined the temporal expression of the various TGF-beta cytokines and their receptors. Purpose: This study sought to determine the temporal mRNA expression of TGF-beta1, TGF-beta2, TGF-beta3, TGFR-I, TGFR-II, Smad-3, and collagen I in a rabbit ear model of hypertrophic scarring compared to smaller, nonhypertrophic control scars. Methods: In an established model of hypertrophic scarring, 7 mm (hypertrophic) and 5 mm (nonhypertrophic control) punch wounds were made on the ears of 12 rabbits. Wounds were harvested at days 7, 15, 28, and 40. Histologic evaluation was performed on all scars in order to validate the model. Real-time RT-PCR was performed to compare mRNA expression between the various time points. Results: At day 7, the 5 mm wounds had epithelialized to a greater extent than the 7 mm wounds. At day 28 and 40, the 7 mm scars were hypertrophic compared to the 5 mm control scars. In both 7 mm and 5 mm scars, TGF-beta1 and beta3 levels declined over time. In 7 mm scars, TGF-beta2 peaked at day 28, TGFR-I levels peaked at day 15, and TGFR-II and Smad-3 remained stable over time. As expected, collagen I expression peaked at day 28. In the 5 mm scars, TGF-beta2 levels remained stable, TGFR-I levels peaked at day 28, while levels of TGFR-II and Smad-3 declined slightly over time. Collagen I expression peaked at day 15. Conclusions: The up-regulation of TGF-beta2 mRNA expression in hypertrophic but not flat scars indicates that it may be important to scar hypertrophy. The sustained expression of TGFR-II and Smad-3 in hypertrophic scars compared to controls suggests that the role of the TGF-beta family in the process of hypertrophic scarring is complex. This study was supported by an NIH grant (5R01GM063825-03) awarded to T.A. Mustoe.