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  • The EMBO Journal (1999) 18, 5205 - 5215
  • doi:10.1093/emboj/18.19.5205

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

Barbara Munz1,2, Hans Smola3, Felix Engelhardt1,4, Kerstin Bleuel1, Maria Brauchle1,5, Iris Lein1, Lee W. Evans6, Danny Huylebroeck7, Rudi Balling8 and Sabine Werner1,4,9

  1. Max-Planck-Institute of Biochemistry, Am Klopferspitz 18a, 82152 Martinsried, Germany
  2. Present address: Department of Molecular Pharmacology, Stanford University Medical School, 300 Pasteur Drive, Stanford, CA 94305-5332, USA
  3. Klinik für Dermatologie und Venerologie, J.-Stelzmann-Strasse 9, 50924 Köln, Germany
  4. Institute of Cell Biology, Swiss Federal Institute of Technology, ETH-Hönggerberg, 8093 Zürich, Switzerland
  5. Present address: Novartis Pharma AG, 4002 Basel, Switzerland
  6. School of Biological and Molecular Sciences, Oxford Brookes University, Headington, Oxford OX3 0BP, UK
  7. Department of Cell Growth, Differentiation and Development (VIB07), Flanders Interuniversity Institute for Biotechnology (VIB) and Laboratory of Molecular Biology (CELGEN), University of Leuven, Herestraat 49, B-3000 Leuven, Belgium
  8. GSF Forschungszentrum für Umwelt und Gesundheit, Institut für Säugetiergenetik, Ingolstädter Landstrasse 1, 85764 Neuherberg, Germany
  9. Institute of Cell Biology, Swiss Federal Institute of Technology, ETH Hönggerberg, CH-8093 Zürich, Switzerland

Correspondence to:

Sabine Werner, E-mail: Sabine.werner@cell.biol.ethz.ch

Received 4 June 1999; Accepted 10 August 1999; Revised 10 August 1999

Recently we demonstrated a strong induction of activin expression after skin injury, suggesting a function of this transforming growth factor-beta family member in wound repair. To test this possibility, we generated transgenic mice that overexpress the activin betaA chain in the epidermis under the control of a keratin 14 promoter. The transgenic mice were significantly smaller than control littermates, and they had smaller ears and shorter tails. 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 significantly increased, and the epidermal architecture was highly disorganized. These histological abnormalities seem to result from increased proliferation of the basal keratinocytes and abnormalities in the program of keratinocyte differentiation. After skin injury, a significant enhancement of granulation 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 fibrosis and cutaneous wound repair.

  • Keywords:

    • activin,
    • epidermis,
    • granulation tissue,
    • keratinocyte,
    • wound