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Overexpression of activin A in the skin of transgenic mice reveals new activities of activin in epidermal morphogenesis, dermal fibrosis and wound repair
Author(s) -
Munz Barbara,
Smola Hans,
Engelhardt Felix,
Bleuel Kerstin,
Brauchle Maria,
Lein Iris,
Evans Lee W.,
Huylebroeck Danny,
Balling Rudi,
Werner Sabine
Publication year - 1999
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/18.19.5205
Subject(s) - biology , epidermis (zoology) , wound healing , keratinocyte , hair follicle , fibrosis , morphogenesis , keratin , fibronectin , microbiology and biotechnology , amphiregulin , genetically modified mouse , pathology , extracellular matrix , transgene , epidermal growth factor , immunology , anatomy , cell culture , gene , genetics , medicine
Recently we demonstrated a strong induction of activin expression after skin injury, suggesting a function of this transforming growth factor‐β family member in wound repair. To test this possibility, we generated transgenic mice that overexpress the activin βA 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.

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