Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing

Y Shirakata, R Kimura, D Nanba… - Journal of cell …, 2005 - journals.biologists.com
Y Shirakata, R Kimura, D Nanba, R Iwamoto, S Tokumaru, C Morimoto, K Yokota…
Journal of cell science, 2005journals.biologists.com
Members of the epidermal growth factor (EGF) family are the most important growth factors
involved in epithelialization during cutaneous wound healing. Heparin-binding EGF-like
growth factor (HB-EGF), a member of the EGF family, is thought to play an important role in
skin wound healing. To investigate the in vivo function of HB-EGF in skin wound healing, we
generated keratinocyte-specific HB-EGF-deficient mice using Cre/loxP technology in
combination with the keratin 5 promoter. Studies of wound healing revealed that wound …
Members of the epidermal growth factor (EGF) family are the most important growth factors involved in epithelialization during cutaneous wound healing. Heparin-binding EGF-like growth factor (HB-EGF), a member of the EGF family, is thought to play an important role in skin wound healing. To investigate the in vivo function of HB-EGF in skin wound healing, we generated keratinocyte-specific HB-EGF-deficient mice using Cre/loxP technology in combination with the keratin 5 promoter. Studies of wound healing revealed that wound closure was markedly impaired in keratinocyte-specific HB-EGF-deficient mice. HB-EGF mRNA was upregulated at the migrating epidermal edge, although cell growth was not altered. Of the members of the EGF family, HB-EGF mRNA expression was induced the most rapidly and dramatically as a result of scraping in vitro. Combined, these findings clearly demonstrate, for the first time, that HB-EGF is the predominant growth factor involved in epithelialization in skin wound healing in vivo and that it functions by accelerating keratinocyte migration, rather than proliferation.
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