title: Does cartilage down-regulate growth factor expression in tracheal epithelium?
abstract: BACKGROUND
  Maintaining tracheal integrity and restoring normal physiologic function after injury is complex. Some of the critical events in this process are deposition of a provisional extracellular matrix, tissue remodeling, and angiogenesis. These events are coordinated with epithelial migration and proliferation to restore the mucosal barrier. The ability of respiratory epithelial cells (REC) to migrate and proliferate and restore denuded areas of the large conducting airway after injury is poor.
  
  
  OBJECTIVE
  To test the hypotheses that (1) the cartilaginous framework, underlying the extracellular matrix (submucosa) and epithelium, decreases the migratory ability of REC when compared with REC on the same provisional extracellular matrix (type I collagen) alone, and (2) this phenomenon is associated with a change in expression of transforming growth factor (TGF)-alpha and TGF-beta, both of which have been demonstrated in cutaneous models to be important in epithelial migration and proliferation.
  
  
  METHODS
  We developed a culture system that reconstitutes the tracheal lumen in vitro, consisting of dissociated chondrocytes cultured in a manner to form cartilage, submucosa (type I collagen), and REC (termed a "composite culture"). Control cultures consisted of epithelial cells grown on type I collagen alone. Control and composite cultures were evaluated morphologically using scanning electron and light microscopy. Expression of TGF-alpha and TGF-beta was determined in day 14 cultured epithelial cells from control and composite cultures by semiquantitative polymerase chain reaction.
  
  
  RESULTS
  Epithelial cells from composite cultures did not spread and were less squamoid in morphological appearance than epithelial cells on type I collagen alone. Expression of both growth factors was reduced in epithelial cells from composite cultures compared with those on type I collagen.
  
  
  CONCLUSIONS
  Cartilage modulates TGF-alpha and TGF-beta expression in REC, and may contribute to regulation of REC proliferation and differentiation.
authors.affiliation: Department of Head and Neck Surgery, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors.forename: W
authors.initials: W
authors.lastname: Hicks
authors.forename: L
authors.initials: L
authors.lastname: Sigurdson
authors.forename: E
authors.initials: E
authors.lastname: Gabalski
authors.forename: R
authors.initials: R
authors.lastname: Hard
authors.forename: L
authors.initials: L
authors.lastname: Hall
authors.forename: J
authors.initials: J
authors.lastname: Gardella
authors.forename: C
authors.initials: C
authors.lastname: Powers
authors.forename: N
authors.initials: N
authors.lastname: Kumar
authors.forename: J
authors.initials: J
authors.lastname: Lwebuga-Mukasa
mesh_terms: D000818:Animals; D002356:Cartilage / Q000378:metabolism*; D002417:Cattle; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism; D003094:Collagen / Q000502:physiology; D046508:Culture Techniques; D015536:Down-Regulation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008855:Microscopy, Electron, Scanning; D018919:Neovascularization, Physiologic / Q000502:physiology; D016133:Polymerase Chain Reaction; D020545:Respiratory Mucosa / Q000166:cytology / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014945:Wound Healing
chemical_list: D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D003094:Collagen