Crucial role of vinexin for keratinocyte migration in vitro and epidermal wound healing in vivo.
In the process of tissue injury and repair, epithelial cells rapidly migrate and form epithelial sheets. Vinexin is a cytoplasmic molecule of the integrin-containing cell adhesion complex localized at focal contacts in vitro. Here, we investigated the roles of vinexin in keratinocyte migration in vitro and wound healing in vivo. Vinexin knockdown using siRNA delayed migration of both HaCaT human keratinocytes and A431 epidermoid carcinoma cells in scratch assay but did not affect cell proliferation. Induction of cell migration by scratching the confluent monolayer culture of these cells activated both EGFR and ERK, and their inhibitors AG1478 and U0126 substantially suppressed scratch-induced keratinocyte migration. Vinexin knockdown in these cells inhibited the scratch-induced activation of EGFR, but not that of ERK, suggesting that vinexin promotes cell migration via activation of EGFR. We further generated vinexin (-/-) mice and isolated their keratinocytes. They similarly showed slow migration in scratch assay. Furthermore, vinexin (-/-) mice exhibited a delay in cutaneous wound healing in both the back skin and tail without affecting the proliferation of keratinocytes. Together, these results strongly suggest a crucial role of vinexin in keratinocyte migration in vitro and cutaneous wound healing in vivo.
Kioka
Noriyuki
N
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Sakyo, Kyoto 606-8502, Japan. nkioka@kais.kyoto-u.ac.jp
Ito
Takuya
T
Yamashita
Hiroshi
H
Uekawa
Natsuko
N
Umemoto
Tsutomu
T
Motoyoshi
Soh
S
Imai
Hiroshi
H
Takahashi
Kenzo
K
Watanabe
Hideto
H
Yamada
Masayasu
M
Ueda
Kazumitsu
K
D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D066246:ErbB Receptors / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D012867:Skin / Q000293:injuries / Q000473:pathology / Q000503:physiopathology; D014945:Wound Healing / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D009124:Muscle Proteins; D034741:RNA, Small Interfering; C486523:SORBS3 protein, human; C117452:Sorbs3 protein, mouse; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases