Abstract |
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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Authors | Yuji Shirakata, Rina Kimura, Daisuke Nanba, Ryo Iwamoto, Sho Tokumaru, Chie Morimoto, Koichi Yokota, Masanori Nakamura, Koji Sayama, Eisuke Mekada, Shigeki Higashiyama, Koji Hashimoto |
Journal | Journal of cell science
(J Cell Sci)
Vol. 118
Issue Pt 11
Pg. 2363-70
(Jun 01 2005)
ISSN: 0021-9533 [Print] England |
PMID | 15923649
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- HBEGF protein, human
- Hbegf protein, mouse
- Heparin-binding EGF-like Growth Factor
- Intercellular Signaling Peptides and Proteins
- RNA, Messenger
- Epidermal Growth Factor
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Topics |
- Animals
- Cell Movement
(genetics, physiology)
- Cell Proliferation
- Cells, Cultured
- Epidermal Growth Factor
(genetics, metabolism)
- Gene Expression Regulation
(genetics, physiology)
- Heparin-binding EGF-like Growth Factor
- Humans
- Intercellular Signaling Peptides and Proteins
- Keratinocytes
(physiology)
- Mice
- Mice, Knockout
- RNA, Messenger
(biosynthesis, genetics)
- Skin
(injuries, metabolism, pathology)
- Wound Healing
(genetics, physiology)
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