Department of Otorhinolaryngology-Head and Neck Surgery, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Otorhinolaryngology Hospital, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Allergy. 2019 Apr;74(4):731-742. doi: 10.1111/all.13647. Epub 2018 Nov 18.
Hippo-Yes-associated protein (YAP) pathway plays an important role in epithelial cell proliferation and development. However, its possible role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains unknown. We aim to investigate it on nasal epithelial proliferation and remodeling in CRSwNP.
The expressions of hippo pathway components as well as Ki-67 and E-cadherin in the sinonasal mucosa and nasal epithelial cells were analyzed in 14 controls, 14 eosinophilic CRSwNP, and 14 noneosinophilic CRSwNP. Nasal epithelial cells from 6 controls, 6 eosinophilic CRSwNP, and 6 noneosinophilic CRSwNP were cultured and treated with lipopolysaccharide (LPS), Poly(I:C), or a selective YAP inhibitor verteporfin (VP).
The hippo pathway components MST1, LATS1/2, YAP, and TEAD1 were increased in both eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells, along with upregulation of Ki-67 and downregulation of E-cadherin. The mRNA levels of YAP positively correlated with the Ki-67 mRNA levels, and negatively associated with the E-cadherin mRNA levels in polyp tissues and epithelial cells from nasal polyps (NPECs). LPS and Poly(I:C) upregulated the YAP expression in nasal epithelial cells accompanied by increased TEAD1 and Ki-67 expression. Conversely, YAP inhibition by VP decreased TEAD1 and Ki-67 expression in NPECs.
Hippo pathway components are abnormally upregulated in NPECs, and its effector YAP promotes nasal epithelial cells proliferation and remodeling in CRSwNP. It provides a rationale to explore inhibition of YAP as a novel therapeutic strategy for reducing the epithelial proliferation and remodeling in CRSwNP.
Hippo-Yes 相关蛋白（YAP）通路在上皮细胞增殖和发育中发挥重要作用。然而，其在慢性鼻-鼻窦炎伴鼻息肉（CRSwNP）中的作用尚不清楚。我们旨在研究其在 CRSwNP 中对鼻上皮增殖和重塑的影响。
在 14 例对照、14 例嗜酸性粒细胞性 CRSwNP 和 14 例非嗜酸性粒细胞性 CRSwNP 患者的鼻黏膜和鼻上皮细胞中分析 Hippo 通路成分以及 Ki-67 和 E-钙黏蛋白的表达。培养 6 例对照、6 例嗜酸性粒细胞性 CRSwNP 和 6 例非嗜酸性粒细胞性 CRSwNP 的鼻上皮细胞，并分别用脂多糖（LPS）、聚肌苷酸：聚胞苷酸（Poly(I:C)）或选择性 YAP 抑制剂维替泊芬（VP）处理。
在嗜酸性粒细胞性和非嗜酸性粒细胞性 CRSwNP 中，Hippo 通路成分 MST1、LATS1/2、YAP 和 TEAD1 均增加，尤其是在上皮细胞中，同时 Ki-67 上调，E-钙黏蛋白下调。息肉组织和鼻息肉上皮细胞（NPECs）中 YAP 的 mRNA 水平与 Ki-67 mRNA 水平呈正相关，与 E-钙黏蛋白 mRNA 水平呈负相关。LPS 和 Poly(I:C) 上调了鼻上皮细胞中 YAP 的表达，同时上调了 TEAD1 和 Ki-67 的表达。相反，VP 抑制 YAP 降低了 NPECs 中 TEAD1 和 Ki-67 的表达。
Hippo 通路成分在上皮细胞中异常上调，其效应因子 YAP 促进 CRSwNP 中鼻上皮细胞的增殖和重塑。这为探索抑制 YAP 作为减少 CRSwNP 上皮细胞增殖和重塑的新治疗策略提供了依据。
