Evaluation of YAP signaling in a rat tympanic membrane under a continuous negative pressure load and in human middle ear cholesteatoma.

OBJECTIVES: Mechanotransduction plays an important role in cell-proliferative activities. Negative pressure in the middle ear is thought to be an important factor related to the etiology of acquired middle ear cholesteatoma. However, the correlation between negative pressure in the middle ear and the mechanism of middle ear cholesteatoma formation remains unclear. In this study, we investigated the expression of key molecules for mechanotransduction immunohistochemically. METHODS: An immunohistochemical analysis was performed using anti-Wnt5a (a marker of alternative Wnt signaling), -Yes-associated protein (YAP) (a marker of mechanosensing) and -pYAP (phosphorylated YAP at Ser 127: inactivated YAP) antibody in the tympanic membrane (TM) under a negative pressure load and in human middle ear cholesteatoma tissues. RESULTS: The number of Wnt5a-positive cells had increased and YAP nuclear translocation was observed in epithelial and mesenchymal cells in the pars flaccida (PF) of the TM under a negative-pressure load and in human middle ear cholesteatoma tissues. CONCLUSIONS: We demonstrated that negative pressure in the middle ear might possibly induce cell proliferation PF of TM in response to mechanical force (mechanotransduction) through YAP nuclear translocation mediated by alternative Wnt signaling, thus affecting human middle ear cholesteatoma formation.