Department of Otorhinolaryngology, Jikei University School of Medicine.
Department of Otorhinolaryngology, Toho University School of Medicine, Tokyo, Japan.
Curr Opin Otolaryngol Head Neck Surg. 2020 Oct;28(5):291-295. doi: 10.1097/MOO.0000000000000655.
Middle ear cholesteatoma is an epithelial lesion that expands into the middle ear, resulting in bone destruction. However, the pathogenesis of this has been unknown. The purpose of this review is to understand the role of keratinocyte growth factor (KGF) during epithelial stem and/or progenitor cell proliferation in middle ear cholesteatoma.
Many researchers have investigated the molecular mechanism of middle ear cholesteatoma to establish a conservative treatment. Recently, some studies have focused on the stem cells of middle ear cholesteatoma and their detection, but the key molecules for stem cell formation were not shown.
We established an animal model for middle ear cholesteatoma and are showing the results of our studies. KGF expression accelerates the proliferation of stem/progenitor cells through the induction of transcription factor p63 expression in the epithelium of the tympanic membrane and mucosal epithelium overlying the promontory of the cochlea and within the attic. This is typical in middle ear cholesteatoma. Moreover, the partial epithelial-mesenchymal transition under the p63 signaling pathway plays an essential role in epithelial cell growth in middle ear cholesteatoma formation. Understanding p63 expression following KGF expression and associated signaling events can improve therapeutic outcomes in patients with middle ear cholesteatoma.
中耳胆脂瘤是一种上皮病变，向中耳扩展，导致骨质破坏。然而，其发病机制尚不清楚。本综述旨在了解角质细胞生长因子（KGF）在中耳胆脂瘤上皮干细胞和/或祖细胞增殖中的作用。
许多研究人员研究了中耳胆脂瘤的分子机制，以建立保守治疗方法。最近，一些研究集中在中耳胆脂瘤的干细胞及其检测上，但没有显示干细胞形成的关键分子。
我们建立了中耳胆脂瘤的动物模型，并展示了我们的研究结果。KGF 通过诱导鼓膜和耳蜗鼓岬覆盖的黏膜上皮中的转录因子 p63 表达，加速了干细胞/祖细胞的增殖，这在中耳胆脂瘤中很典型。此外，p63 信号通路下的部分上皮-间充质转化在中耳胆脂瘤形成中上皮细胞生长中起重要作用。了解 KGF 表达后 p63 的表达及其相关信号事件可以改善中耳胆脂瘤患者的治疗效果。
