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 factor 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 this question we overexpressed the soluble activin antagonist follistatin in the epidermis of transgenic mice. These animals were born with open eyes, and the adult mice had larger ears, longer tails and reduced body weight compared with non-transgenic littermates. Their skin was characterized by a mild dermal and epidermal atrophy. After injury, a severe delay in wound healing was observed. In particular, granulation tissue formation was significantly reduced, leading to a major reduction in wound breaking strength. The wounds, however, finally healed, and the resulting scar area was smaller than in control animals. These results implicate an important function of endogenous activin in the control of wound repair and scar formation.
Wankell
M
M
Institute of Cell Biology, ETH Zürich, Hönggerberg, CH-8093 Zürich, Switzerland.
Munz
B
B
Hübner
G
G
Hans
W
W
Wolf
E
E
Goppelt
A
A
Werner
S
S
D028341:Activins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis; D002454:Cell Differentiation; D002455:Cell Division; D003001:Cloning, Molecular; D004423:Ear / Q000002:abnormalities; D004817:Epidermis; D038681:Follistatin; D005786:Gene Expression Regulation; D006133:Growth Substances / Q000096:biosynthesis* / Q000235:genetics; D015603:Keratinocytes / Q000166:cytology; D051379:Mice; D008822:Mice, Transgenic; D012867:Skin / Q000293:injuries*; D012868:Skin Abnormalities; D012879:Skin Physiological Phenomena; D019076:Transgenes; D014945:Wound Healing / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; D038681:Follistatin; D006133:Growth Substances; D028341:Activins