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-β (TGF-β) 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-β1 and collagen Iα2 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-β2 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-β1, and possibly TGF-β2, are associated with hypertrophic scar formation.

Abbreviations and Acronyms: PCR, polymerase chain reaction, SEI, scar elevation index, TBR-I, transforming growth factor-β receptor I, TBR-II, transforming growth factor-β receptor II, TGF-β, transforming growth factor-β