Evaluation of YAP signaling in a rat tympanic membrane under a continuous negative pressure load and in human middle ear cholesteatoma
Evaluation of YAP signaling in a rat tympanic membrane under a continuous negative pressure load and in human middle ear cholesteatoma
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DOI：
10.1080/00016489.2017.1351040
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发表时间：
2017-01-01
影响因子：
1.4
通讯作者：
Kojima, Hiromi
中科院分区：
文献类型：
--
作者：
Akiyama, Naotaro;Yamamoto-Fukuda, Tomomi;Kojima, Hiromi
目的：机械转导在细胞增殖活动中起重要作用。中耳负压被认为是后天性中耳胆脂瘤发病的重要因素。然而，中耳负压与中耳胆脂瘤形成机制的相关性尚不清楚。在本研究中，我们用免疫组织化学方法研究了机械转导关键分子的表达。方法：在负压负荷下鼓膜和中耳胆脂瘤组织中使用抗wnt5a（替代Wnt信号的标志物）、- ye相关蛋白（YAP）（机械感测标志物）和-pYAP （Ser 127位点磷酸化YAP：失活YAP）抗体进行免疫组织化学分析。结果：在负压负荷下，人中耳胆脂瘤组织和TM松弛部（PF）上皮细胞和间充质细胞中wnt5a阳性细胞数量增加，YAP核易位。结论：我们证明了中耳负压可能通过Wnt替代信号介导的YAP核易位，诱导TM细胞增殖PF响应机械力（机械转导），从而影响人中耳胆脂瘤的形成。
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.