Heparin-binding EGF-like growth factor accelerates keratinocyte migration and skin wound healing.
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.
Shirakata
Yuji
Y
Department of Dermatology, Ehime University School of Medicine, Ehime 791-0295, Japan. shirakat@m.ehime-u.ac.jp
Kimura
Rina
R
Nanba
Daisuke
D
Iwamoto
Ryo
R
Tokumaru
Sho
S
Morimoto
Chie
C
Yokota
Koichi
K
Nakamura
Masanori
M
Sayama
Koji
K
Mekada
Eisuke
E
Higashiyama
Shigeki
S
Hashimoto
Koji
K
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*
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