Notch Signaling in Acquired Middle Ear Cholesteatoma
Notch Signaling in Acquired Middle Ear Cholesteatoma
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Notch信号在获得性中耳胆脂瘤中的作用
DOI：
10.1097/mao.0000000000003245
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发表时间：
2021-10-01
影响因子：
2.1
通讯作者：
Homma, Akihiro
中科院分区：
文献类型：
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作者：
Fukuda, Atsushi;Kano, Satoshi;Homma, Akihiro
假设：我们假设Notch信号的异常变化可能与胆脂瘤的病理生理学有关。背景：Notch 信号通路调节角质形成细胞的综合生长和分化控制。它与胆脂瘤增殖的关系尚未阐明。方法：我们从接受鼓乳突手术的中耳胆脂瘤患者中获取了胆脂瘤和外耳道（EAC）皮肤样本。我们使用 RT2 Profiler (TM) PCR Array Human Notch Signaling Pathway (Qiagen) 对胆脂瘤和 EAC 皮肤样本（各 n = 6）进行聚合酶链反应。随后分别对 41 份和 8 份胆脂瘤和 EAC 皮肤样本中的 Notch1、split-1 增强子 (HES1) 和 p53 进行免疫组织化学染色。结果：Notch1基因表达倍数变化在胆脂瘤中最低，具有统计学显着性差异(p = 0.0424)。此外，HES1 表达的倍数变化降低 (p = 0.272)。胆脂瘤中Notch1和HES1蛋白表达的阳性率（分别为48.5±32.4％和44.9±17.8％）显着低于EAC皮肤中（分别为83.4±17.5％和55.7±7.1％）（p < 0.01）。相反，胆脂瘤中p53表达的阳性率（8.5+/-11.4%）显着高于EAC皮肤中的（0.5+/-0.7%）（p<0.001）。结论：Notch1和HES1蛋白表达的降低可能在胆脂瘤角化鳞状上皮的过度增殖特征中发挥重要作用。 p53 的增加可能反映了对细胞过度增殖的反应。
Hypothesis: We hypothesized that an anomalous change of Notch signaling might be involved in the pathophysiology of cholesteatoma. Background: The Notch signaling pathway regulates integrated growth and differentiation control of keratinocytes. Its involvement in cholesteatoma proliferation has not been elucidated. Methods: We obtained cholesteatoma and external auditory canal (EAC) skin samples from patients with middle ear cholesteatoma who underwent tympanomastoid surgery. We performed polymerase chain reaction using the RT2 Profiler (TM) PCR Array Human Notch Signaling Pathway (Qiagen) in the cholesteatoma and EAC skin samples (n = 6 each). This was followed by immunohistochemical staining of Notch1, enhancer of split-1 (HES1), and p53 in 41 and 8 cholesteatoma and EAC skin samples, respectively. Results: The fold change of Notch1 gene expression was lowest in cholesteatoma, with a statistically significant difference (p = 0.0424). Moreover, the fold change of HES1 expression decreased (p = 0.272). The positive rates of Notch1 and HES1 protein expressions in the cholesteatoma (48.5 +/- 32.4% and 44.9 +/- 17.8%, respectively) were significantly lower than in the EAC skin (83.4 +/- 17.5% and 55.7 +/- 7.1%, respectively) (p p < 0.01). In contrast, the positive rate of p53 expression in the cholesteatoma (8.5 +/- 11.4%) was significantly higher than in the EAC skin (0.5 +/- 0.7%) (p < 0.001). Conclusion: The decreases in Notch1 and HES1 protein expression might play an important role in the hyperproliferative character of the keratinizing squamous epithelium in cholesteatoma. An increase in p53 might reflect the reaction to cellular hyperproliferation.