Retinoic Acid Depletion Induces Keratinizing Squamous Differentiation in Human Middle Ear Epithelial Cell Culture / 대한이비인후과학회지

ABSTRACT

BACKGROUND AND OBJECTIVES: 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 the association. This study was undertaken to investigate whether normal human middle ear epithelial (NHMEE) cells undergo keratinizing squamous differentiation in retinoic acid (RA)-deficient culture. MATERIALS AND METHOD: We examined the morphological differences between RA-deficient and RA-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 culture. In addition, the expressions of mucin gene 5AC (MUC5AC) and MUC8 mRNA were suppressed, and the expression of cornifin-alpha mRNA increased progressively as a function of differentiation in RA-deficient culture. CONCLUSION: Our study shows that RA depletion induces keratinizing squamous differentiation in NHMEE cell culture.