title: Increased fragility, impaired differentiation, and acceleration of migration of corneal epithelium of epiplakin-null mice.
abstract: OBJECTIVE
  To investigate the effects of gene ablation of epiplakin on the homeostasis of corneal epithelium in mice.
  
  
  METHODS
  Light and transmission electron microscopic histology, immunohistochemistry, and real-time RT-PCR were carried out to evaluate the effects of the loss of epiplakin on structure and gene expression of cell-cell adhesion-related components in mice. Integrity against mechanical intervention and wound-healing response of corneal epithelium were also tested.
  
  
  RESULTS
  Epiplakin protein was detected in the cells of the basal layer of corneal epithelium. Morphologically basal-like cells were observed in the suprabasal layer of adult epiplakin-null corneal epithelium, suggesting an impaired intraepithelial cell differentiation. Such abnormality was not detected in mice before the age of postnatal day 14. Epiplakin-deficient epithelium exhibits fragility against mechanical intervention as compared with wild-type epithelium. Although cell proliferation is suppressed, migration-dependent wound healing is promoted in epiplakin-null epithelium. E-cadherin expression was suppressed by the loss of epiplakin in the epithelium.
  
  
  CONCLUSIONS
  Lacking epiplakin affects cell differentiation of the corneal epithelium, as well as its proliferation activity and its structural integrity. The mechanism of acceleration of cell migration in the epiplakin-null corneal epithelium is to be further investigated, although suppression of expression of E-cadherin might be included.
authors.affiliation: Department of Ophthalmology, Wakayama Medical University School of Medicine, Wakayama, Japan. kokado@wakayama-med.ac.jp
authors.forename: Masahide
authors.initials: M
authors.lastname: Kokado
authors.forename: Yuka
authors.initials: Y
authors.lastname: Okada
authors.forename: Mizuki
authors.initials: M
authors.lastname: Goto
authors.forename: Kazushi
authors.initials: K
authors.lastname: Ishikawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Miyamoto
authors.forename: Osamu
authors.initials: O
authors.lastname: Yamanaka
authors.forename: Sakuhei
authors.initials: S
authors.lastname: Fujiwara
authors.forename: Shizuya
authors.initials: S
authors.lastname: Saika
mesh_terms: D000818:Animals; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D019573:Epithelium, Corneal / Q000473:pathology* / Q000503:physiopathology* / Q000648:ultrastructure; D006706:Homeostasis / Q000502:physiology; D007365:Intercellular Junctions / Q000473:pathology / Q000502:physiology / Q000648:ultrastructure; D007382:Intermediate Filaments / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D012333:RNA, Messenger / Q000378:metabolism; D014945:Wound Healing / Q000502:physiology
chemical_list: D001324:Autoantigens; D012333:RNA, Messenger; C426678:epiplakin
keywords: corneal epithelium; differentiation; epiplakin; fragility; knockout; mouse; wound healing