title: Slug is upregulated during wound healing and regulates cellular phenotypes in corneal epithelial cells.
abstract: OBJECTIVE
  The involvement of the epithelial mesenchymal transition (EMT) in the process of corneal wound healing remains largely unclear. The purpose of the present study was to gain insight into Slug expression and corneal wound healing.
  
  
  METHODS
  Slug expression during wound healing in the murine cornea was evaluated using fluorescence staining in vivo. Slug or Snail was stably introduced into human corneal epithelial cells (HCECs). These stable transfectants were evaluated for the induction of the EMT, cellular growth, migration activity, and expression changes in differentiation-related molecules.
  
  
  RESULTS
  Slug, but not Snail, was clearly expressed in the nuclei of corneal epithelial cells in basal lesion of the corneal epithelium during wound healing in vivo. The overexpression of Slug or Snail induced an EMT-like cellular morphology and cadherin switching in HCECs, indicating that these transcription factors were able to mediate the typical EMT in HCECs. The overexpression of Slug or Snail suppressed cellular proliferation but enhanced the migration activity. Furthermore, ABCG2, TP63, and keratin 19, which are known as stemness-related molecules, were downregulated in these transfectants.
  
  
  CONCLUSIONS
  It was found that Slug is upregulated during corneal wound healing in vivo. The overexpression of Slug mediated a change in the cellular phenotype affecting proliferation, migration, and expression levels of differentiation-related molecules. This is the first evidence that Slug is regulated during the process of corneal wound healing in the corneal epithelium in vivo, providing a novel insight into the EMT and Slug expression in corneal wound healing.
authors.affiliation: Department of Ophthalmology, Kinki University Faculty of Medicine, Osaka, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Aomatsu
authors.forename: Tokuzo
authors.initials: T
authors.lastname: Arao
authors.forename: Kosuke
authors.initials: K
authors.lastname: Abe
authors.forename: Aya
authors.initials: A
authors.lastname: Kodama
authors.forename: Koji
authors.initials: K
authors.lastname: Sugioka
authors.forename: Kazuko
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Kanae
authors.initials: K
authors.lastname: Kudo
authors.forename: Hideharu
authors.initials: H
authors.lastname: Kimura
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fujita
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hayashi
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Nagai
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Shimomura
authors.forename: Kazuto
authors.initials: K
authors.lastname: Nishio
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002465:Cell Movement; D004195:Disease Models, Animal; D019573:Epithelium, Corneal / Q000293:injuries / Q000378:metabolism / Q000473:pathology*; D005131:Eye Injuries / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D015854:Up-Regulation; D014945:Wound Healing / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; C000604407:SNAI1 protein, human; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors