Increased expression of β6-integrin in skin leads to spontaneous development of chronic wounds

L Häkkinen, L Koivisto, H Gardner… - The American journal of …, 2004 - Elsevier
L Häkkinen, L Koivisto, H Gardner, U Saarialho-Kere, JM Carroll, M Lakso, H Rauvala…
The American journal of pathology, 2004Elsevier
Integrin αvβ6 is an epithelial cell-specific receptor that is not normally expressed by resting
epithelium but its expression is induced during wound healing. The function of αvβ6-integrin
in wound repair is not clear. In the present study, we showed that β6-integrin expression was
strongly up-regulated in the epidermis in human chronic wounds but not in different forms of
skin fibrosis. To test whether increased β6-integrin expression plays a role in abnormal
wound healing we developed four homozygous transgenic mouse lines that constitutively …
Integrin αvβ6 is an epithelial cell-specific receptor that is not normally expressed by resting epithelium but its expression is induced during wound healing. The function of αvβ6-integrin in wound repair is not clear. In the present study, we showed that β6-integrin expression was strongly up-regulated in the epidermis in human chronic wounds but not in different forms of skin fibrosis. To test whether increased β6-integrin expression plays a role in abnormal wound healing we developed four homozygous transgenic mouse lines that constitutively expressed human β6-integrin in the epithelium. The mice developed normally and did not show any histological abnormalities in the skin. The rate of experimental skin wound closure was unaltered and the wounds healed without significant scar formation. However, during breeding program 16.1 to 27.0% of transgenic mice developed spontaneous, progressing fibrotic chronic ulcers. None of the wild-type animals developed these lesions. The chronic lesions had areas with severe fibrosis and numerous activated macrophages and fibroblasts expressing transforming growth factor (TGF)-β. The level of TGF-β1 was significantly increased in the lesions as compared with normal skin. The findings suggest that increased αvβ6-integrin in keratinocytes plays an active part in abnormal wound healing possibly through a mechanism involving increased activation of TGF-β.
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