Modulatory Effect of TGF-beta 2 to Proliferative Kinetics of Fibroblast in Keloid and Hypertrophic Scar

Kim, Young Jin

Abstract

Keloid and hypertrophic scar are dermal fibroproliferative disorders characterized by an overabundant deposition of collagen. Recently these dermal proliferative disorders have been linked clinically to the cytokine transforming growth factor beta(TGF-beta), and in vitro tests have shown it to be responsible for the activation of fibroblasts and their production and deposition of collagen. By using an established in vivo animal model of proliferative scarring, these scars were examined. Proliferative scar specimens were implanted into athymic, asplenic nude rats and isolated in sandwich island flap based on the superficial inferior epigastric pedicle. After establishment of the transferred flap, the scars were injected with varying doses of TGF-beta 2 or vehicle for 5 consecutive days and then again on days 10, 15, and 20. The specimens were measured weekly during the period of dosing, and a biopsy was acquired on days 30 and 60. Fibroblasts from the explanted biopsies and the original scars were grown in cell culture, and cell proliferation studies were performed and the results compared. There was a dose response to TGF-beta 2, with 200ng showing the greatest effect. From the original scar specimens, keloid scars demonstrated the greatest cell proliferation kinetics-significantly faster than hypertrophic scars. After treatment with TGF-beta 2, keloids showed an increase in their cell proliferation kinetics compared with vehicle alone. This was not demonstrated with the hypertrophic scars. Elevated levels of TGF-beta 2 are a major contributing factor to the process of proliferative scars, but because hypertrophic scars do not result in an equally increased response to this cytokine, a truly causative role for this cytokine cannot be promulgated. Rather, it is rather combination of the proliferative scar fibroblasts' abnormal response to TGF-beta 2 stimulation and elevated levels of this cytokine that controls more accurately the process of keloid formation.