title: Repair of naphthalene-induced acute tracheal injury by basal cells depends on β-catenin.
abstract: OBJECTIVE
  Little is known about the role of Wnt/β-catenin in postnatal airway homeostasis and basal cell function. This study aimed to investigate the role of Wnt signaling in the self-renewal of basal cells and the involvement of β-catenin in tracheal repair after naphthalene-induced injury.
  
  
  METHODS
  Mice were treated with naphthalene and injected with 4-hydroxytamoxifen. Injury and repair of the tracheal epithelium after naphthalene-mediated secretory cell depletion was assessed by a immunohistochemical study. The involvement of Wnt and β-catenin signaling in basal cell proliferation was investigated during in vitro expansion.
  
  
  RESULTS
  Immunohistochemical analysis of tracheal epithelium in wild-type mice showed a reduction in the number of Clara cell secretory protein (CCSP+) and forkhead box transcription factor (Fox-J1+) cells on days 2 to 5 after naphthalene-induced injury; this cell population was regenerated by day 10. After flush labeling, bromodeoxyuridine-positive (BrdU+) cells and Ki67+ cells were observed in tracheal epithelium on days 2 to 5 but not on days 10 and 21. Confocal microscopy visualizing K5+ and BrdU+ cells showed that Wnt3a promotes proliferation of K5+ cells. Immunohistochemical analysis of K5+ and CCSP+ in tracheal epithelial cells from wild-type littermate and K5-Cre-mediated β-catenin knock-out mice showed that on day 3, the number of CCSP+ cells was decreased in all mice. On day 10, CCSP+ cells were present in wild-type littermate mice but absent in conditional knock-out mice.
  
  
  CONCLUSIONS
  Basal cells serve as stem cells in the tracheal epithelium, regenerating and maintaining tracheal epithelial cells in a mouse model of tracheal injury. β-Catenin is required for proliferation and self-renewal of tracheal epithelial cells.
authors.affiliation: Institute of Emergency and Critical Care Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Division of Thoracic Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan. Electronic address: hsuhs@vghtpe.gov.tw.
authors.forename: Han-Shui
authors.initials: HS
authors.lastname: Hsu
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Chen-Chi
authors.initials: CC
authors.lastname: Liu
authors.affiliation: Institute of Emergency and Critical Care Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Jiun-Han
authors.initials: JH
authors.lastname: Lin
authors.affiliation: Institute of Emergency and Critical Care Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Tien-Wei
authors.initials: TW
authors.lastname: Hsu
authors.affiliation: Institute of Emergency and Critical Care Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan.
authors.forename: Kelly
authors.initials: K
authors.lastname: Su
authors.affiliation: Institute of Clinical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan; Stem Cell Laboratory, Department of Medical Research and Education, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan. Electronic address: hungsc@vghtpe.gov.tw.
authors.forename: Shih-Chieh
authors.initials: SC
authors.lastname: Hung
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D053569:Keratin-15; D053555:Keratin-5 / Q000235:genetics / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009281:Naphthalenes / Q000633:toxicity*; D012038:Regeneration / Q000187:drug effects*; D020545:Respiratory Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014598:Uteroglobin / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C495267:CTNNB1 protein, mouse; C481963:FOXJ1 protein, mouse; D051858:Forkhead Transcription Factors; D053569:Keratin-15; D053555:Keratin-5; D019394:Ki-67 Antigen; C492053:Krt15 protein, mouse; D009281:Naphthalenes; C556390:Scgb1a1 protein, mouse; D051176:beta Catenin; C031721:naphthalene; D014598:Uteroglobin