Abnormal Expression of YAP Is Associated With Proliferation, Differentiation, Neutrophil Infiltration, and Adverse Outcome in Patients With Nasal Inverted Papilloma

作者：Yuan Tian, Rui Zheng, Xiang‐Min Zhou, Peng Jin, Zhi‐Qun Huang, Xiaoxue Zi, Qingwu Wu, Weihao Wang, Hui-yi Deng, Weifeng Kong, Huijun Qiu, Suizi Zhou, Chen Qian-min, Yanyi Tu, Tao Li, Jing Liu, Kai Sen Tan, Hsiao Hui Ong, Li Shi, Zhuang‐Gui Chen, Xuekun Huang, Qin-tai Yang, De Yun Wang · 发表于：Frontiers in Cell and Developmental Biology · 年份：2021 · DOI：10.3389/fcell.2021.625251 · 被引用次数：9 · 研究领域：Head and Neck Surgical Oncology、Sinusitis and nasal conditions、Hippo pathway signaling and YAP/TAZ

Background Nasal inverted papilloma (NIP) is a common benign tumor. Yes-associated protein (YAP) is the core effector molecule of the Hippo pathway, which regulates the proliferation and differentiation of airway epithelium. While its role in proliferation may be connected to NIP formation, no definitive association has been made between them. Methods We compared the difference of YAP expression and proliferation level between the control inferior turbinate, NP (nasal polyps), and NIP groups. In addition, we further used PCR, immunofluorescence, and immunohistochemistry to investigate YAP’s role in the proliferation and differentiation of the nasal epithelium and inflammatory cell infiltration, correlating them with different grades of epithelial remodeling. We further used an IL-13 remodeling condition to investigate YAP’s role in differentiation in an in vitro air-liquid interface (ALI) human nasal epithelial cell (hNECs) model. Finally, we also explored the correlation between YAP expression and clinical indicators of NIP. Results The expression of YAP/active YAP in the NIP group was significantly higher than that in the NP group and control group. Moreover, within the NIP group, the higher grade of epithelial remodeling was associated with higher YAP induced proliferation, leading to reduced ciliated cells and goblet cells. The finding was further verified using an IL-13 remodeling condition in differentiating ALI hNECs. Furthermore, YAP expression was positively correlat...