In the dynamic and complex process of wound healing, locally produced growth factors are important mediators, although their actual roles have not been fully established. In the present study, the presence of transforming growth factor-β1 and -α during the re-epithelialization of full-thickness wounds was investigated in an in vitro model of wound healing in human skin. The amounts of transforming growth factor-β1 and -α secreted from the wound area were measured with enzyme immunoassays, and immunohistochemistry was used to study the localization of these two growth factors in the healing wound. The wounds were followed until they were completely re-epithelialized. The results showed a continuous increase in secreted transforming growth factor-β1 throughout the re-epithelialization phase of healing followed by a decrease after its completion. The keratinocytes migrating out from the wound edges showed intense staining for transforming growth factor-β1 which declined to the level of the surrounding epidermis after the wound was covered by a new epidermis. After the skin was wounded, a decrease both in secreted transforming growth factor-α and in immunostaining for this growth factor was apparent. Even though a minor increase in the immunoreactivity for transforming growth factor-α occurred after the completion of re-epithelialization, no increase in secreted transforming growth factor-α could be detected by enzyme immunoassay. These data suggest that keratinocytes modulate their expression of transforming growth factor-β1 and -α during the wound healing process in human skin and that these changes may be controlled in part by autocrine pathways.
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