Expression and function of keratinocyte growth factor and activin in skin morphogenesis and cutaneous wound repair

Reepithelialization and granulation tissue formation during cutaneous wound repair are mediated by a wide variety of growth and differentiation factor s. Recent studies from our laboratory provided evidence for an important ro le of keratinocyte growth factor (KGF) in the repair of the injured epithel ium and for a novel function of the transforming growth factor-beta superfa mily member activin in granulation tissue formation, KGF is weakly expresse d in human skin, but is strongly upregulated in dermal fibroblasts after sk in injury. Its binding to a transmembrane receptor on keratinocytes induces proliferation and migration of these cells. Furthermore, KGF has been show n to protect epithelial cells from the toxic effects of reactive oxygen spe cies. We have identified a series of KGF-regulated genes that are Likely to play a role in these processes, In addition to KGF, activin seems to be a novel player in wound healing. Activin expression is hardly detectable in n onwounded skin, but this factor is highly expressed in redifferentiating ke ratinocytes of the hyperproliferative wound epithelium as well as in cells of the granulation tissue. To gain insight into the role of activin in woun d repair, we generated transgenic mice that overexpress activin in basal ke ratinocytes of the epidermis, These mice were characterized by a hyperthick ened epidermis and by dermal fibrosis, Most importantly, overexpression of activin strongly enhanced the process of granulation tissue formation, demo nstrating a novel and important role of activin in cutaneous wound repair.