title: Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing.
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.
authors.affiliation: Department of Dermatology, Ehime University School of Medicine, Ehime 791-0295, Japan. shirakat@m.ehime-u.ac.jp
authors.forename: Yuji
authors.initials: Y
authors.lastname: Shirakata
authors.forename: Rina
authors.initials: R
authors.lastname: Kimura
authors.forename: Daisuke
authors.initials: D
authors.lastname: Nanba
authors.forename: Ryo
authors.initials: R
authors.lastname: Iwamoto
authors.forename: Sho
authors.initials: S
authors.lastname: Tokumaru
authors.forename: Chie
authors.initials: C
authors.lastname: Morimoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Yokota
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakamura
authors.forename: Koji
authors.initials: K
authors.lastname: Sayama
authors.forename: Eisuke
authors.initials: E
authors.lastname: Mekada
authors.forename: Shigeki
authors.initials: S
authors.lastname: Higashiyama
authors.forename: Koji
authors.initials: K
authors.lastname: Hashimoto
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D004815:Epidermal Growth Factor / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology; D066257:Heparin-binding EGF-like Growth Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D015603:Keratinocytes / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012867:Skin / Q000293:injuries / Q000378:metabolism* / Q000473:pathology; D014945:Wound Healing / Q000235:genetics / Q000502:physiology*
chemical_list: C587883:HBEGF protein, human; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D004815:Epidermal Growth Factor