The roles of activins in repair processes of the skin and the brain

Citation
B. Munz et al., The roles of activins in repair processes of the skin and the brain, MOL C ENDOC, 180(1-2), 2001, pp. 169-177
Citations number
52
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
MOLECULAR AND CELLULAR ENDOCRINOLOGY
ISSN journal
0303-7207 → ACNP
Volume
180
Issue
1-2
Year of publication
2001
Pages
169 - 177
Database
ISI
SICI code
0303-7207(20010630)180:1-2<169:TROAIR>2.0.ZU;2-M
Abstract
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.