Temporal Expression of the Transforming Growth Factor-Beta Pathway in the Rabbit Ear Model of Wound Healing and Scarring

BACKGROUND: Despite numerous studies that have investigated the cellular and molecular mechanisms underlying scar formation, this process still remains poorly understood. The importance of transforming growth factor-beta (TGF-beta) in these processes has been well recognized, and this study sought to define the temporal expression of the key members in this pathway in a well-established, clinically relevant, rabbit ear model of hypertrophic scarring. STUDY DESIGN: Seven-millimeter (hypertrophic) and 5-mm (nonhypertrophic) punch wounds were made on the ears of 12 rabbits. Wounds were harvested at days 0, 7, 15, 28, and 40. RESULTS: There were no appreciable histologic differences between the 5- and 7-mm wounds at days 7 and 15. At day 28, however, the 7-mm scars were considerably more hypertrophic compared with the 5-mm control scars (p<0.001). The mRNA levels of TGF-beta1 and collagen Ialpha2 were notably higher in the hypertrophic 7-mm scars at day 28 than in the nonhypertrophic 5-mm scars (p<0.03). Although not pronounced, levels of TGF-beta2 were higher in the hypertrophic scars. There were no other statistically significant differences between the 7- and 5-mm scars. CONCLUSIONS: Elevated levels of TGF-beta1, and possibly TGF-beta2, are associated with hypertrophic scar formation.