title: Retinoic acid depletion induces keratinizing squamous differentiation in human middle ear epithelial cell cultures.
abstract: OBJECTIVE
  The pathogenesis of cholesteatoma behind an intact tympanic membrane remains controversial. Squamous metaplasia of the middle ear mucosa is thought to be a possible mechanism in such cases. However, to date, no definitive experimental results have proved this association. This study was undertaken to investigate whether normal human middle ear epithelial (NHMEE) cells undergo keratinizing squamous differentiation in a retinoic acid (RA)-deficient culture.
  
  
  METHODS
  We examined the morphological differences between RA-deficient and -sufficient cultures, and determined the expressions of the mucin gene and cornifin-alpha mRNAs as indicators of mucous and squamous differentiation, respectively.
  
  
  RESULTS
  Histomorphologically, the NHMEE cells differentiated into a keratinizing squamous epithelium in RA-deficient cultures. In addition, the expressions of mucin gene 5AC (MUCSAC) and MUC8 mRNAs were suppressed, and the expression of cornifin-alpha mRNA increased progressively as a function of differentiation in RA-deficient cultures.
  
  
  CONCLUSIONS
  This study shows that RA depletion induces keratinizing squamous differentiation in NHMEE cell cultures. This finding supports the hypothesis that middle ear cholesteatoma originates from metaplastic middle ear mucosa.
authors.affiliation: Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, South Korea.
authors.forename: Jae Young
authors.initials: JY
authors.lastname: Choi
authors.forename: Kyou-Nam
authors.initials: KN
authors.lastname: Cho
authors.forename: Ki-Han
authors.initials: KH
authors.lastname: Yoo
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Shin
authors.forename: Joo-Heon
authors.initials: JH
authors.lastname: Yoon
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D018424:Cholesteatoma, Middle Ear / Q000209:etiology*; D055233:Cornified Envelope Proline-Rich Proteins; D004432:Ear, Middle / Q000166:cytology* / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis; D009077:Mucins / Q000096:biosynthesis; D009092:Mucous Membrane / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; D008565:Membrane Proteins; D009077:Mucins; D012333:RNA, Messenger; D014212:Tretinoin