Overexpression of activin A in the skin of transgenic mice reveals new activities of activin in epidermal morphogenesis, dermal fibrosis and wound repair

Recently we demonstrated a strong induction of activin expression after ski n injury, suggesting a function of this transforming growth factor-beta fam ily member in wound repair. To test this possibility, we generated transgen ic mice that overexpress the activin beta A chain in the epidermis under th e control of a keratin 14 promoter. The transgenic mice were significantly smaller than control littermates, and they had smaller ears and shorter tai ls. In their skin, the fatty tissue was replaced by connective tissue and a severe thickening of the epidermis was found. The spinous cell layer was s ignificantly increased, and the epidermal architecture was highly disorgani zed. These histological abnormalities seem to result from increased prolife ration of the basal keratinocytes and abnormalities in the program of kerat inocyte differentiation. After skin injury, a significant enhancement of gr anulation tissue formation was detected in the activin-overexpressing mice, possibly as a result of premature induction of fibronectin and tenascin-C expression. These data reveal novel activities of activin in the regulation of keratinocyte proliferation and differentiation as well as in dermal fib rosis and cutaneous wound repair.