A recent study from our laboratory demonstrated a strong upregulation of ac
tivin expression during cutaneous wound healing. To further analyze the rol
e of activin A in skin morphogenesis and wound repair, we generated transge
nic mice that overexpress activin A under the control of the keratin 14 pro
moter. The latter targets expression of transgenes to the basal, proliferat
ing layer of the epidermis. Hetero- as well as homozygous transgenic animal
s were viable and fertile. However, they were smaller than non-transgenic l
ittermates and they had smaller ears and shorter tails. Histological analys
is of their skin revealed dermal hyperthickening, mainly due to the replace
ment of fatty tissue by connective tissue, and an increase in suprabasal, p
artially differentiated epidermal layers. After cutaneous injury, a strong
enhancement of granulation tissue formation was observed. Furthermore, the
extent of re-epithelialization was increased in some of the wounds. These d
ata demonstrate that activin A is a potent stimulator of the wound healing
process. Using an in vivo model of local brain injury, we found that activi
n A also plays a significant role in the early cellular response to neurona
l damage. Expression of activin mRNA and protein is markedly upregulated wi
thin a few hours of injury. If applied exogenously, recombinant activin A i
s capable of rescuing neurons from acute cell death. Studying the interacti
on between bFGF, a well-established neuroprotective agent, which is current
ly being tested in stroke patients, and activin A, we arrived at the unexpe
cted conclusion that it is the strong induction of activin A by bFGF which
endows the latter with its beneficial actions in patients. These findings s
uggest that the development of substances directly targeting activin expres
sion or receptor binding should offer new possibilities in the acute treatm
ent of stroke and brain trauma. (C) 2001 Elsevier Science Ireland Ltd. All
rights reserved.