Impaired wound healing in transgenic mice overexpressing the activin antagonist follistatin in the epidermis

Recently, we demonstrated a strong upregulation of activin expression after skin injury. Furthermore, overexpression of this transforming growth facto r beta family member in the skin of transgenic mice caused dermal fibrosis, epidermal hyperthickening and enhanced wound repair. However, the role of endogenous activin in wound healing has not been determined. To address thi s question we overexpressed the soluble activin antagonist follistatin in t he epidermis of transgenic mice. These animals were born with open eyes, an d the adult mice had larger ears, longer tails and reduced body weight comp ared with nontransgenic littermates. Their skin was characterized by a mild dermal and epidermal atrophy. After injury, a severe delay in wound healin g was observed. In particular, granulation tissue formation was significant ly reduced, leading to a major reduction in wound breaking strength. The wo unds, however, finally healed, and the resulting scar area was smaller than in control animals. These results implicate an important function of endog enous activin in the control of wound repair and scar formation.