Ma Yun, Tian Peng, Zhong Hua, Wu Fan, Zhang Qining, Liu Xiang, Dang Hua, Chen Qiujian, Zou Hua, Zheng Yiqing
Department of Otorhinolaryngology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
Department of Otorhinolaryngology, First Affiliated Hospital of Sun Yat-sen University, Sun Yat-sen University, Guangzhou, China.
Front Cell Dev Biol. 2021 Feb 1;8:630340. doi: 10.3389/fcell.2020.630340. eCollection 2020.
Cilia loss and dysfunction is one of the typical pathological features of chronic rhinosinusitis with nasal polyps (CRSwNP). Tryptophan-aspartic acid (W-D) repeat containing planar cell polarity effector (WDPCP) has been proven to be an essential element for ciliogenesis in human nasal epithelium, but its role in the beating of cilia remains unclear. In this study, we sought to investigate the role of WDPCP and its underlying mechanism behind the dysfunction in the beating of cilia in nasal polyp tissue. We demonstrated WDPCP expression in the epithelium of nasal polyps. We also investigated the MAPK/ERK pathway in primary human sinonasal epithelial cells to explore the function of WDPCP. The air-liquid interface culture system was used as a model to verify the role of WDPCP and the MAPK/ERK pathway in the beating of cilia. With the dysfunction of cilia beating, we observed a low expression of WDPCP in the epithelium of nasal polyp tissues. Within the study, we found that WDPCP was critical for mitochondrial biogenesis and mitochondrial function in human sinonasal epithelial cells, possibly due to the activation of the MAPK/ERK pathway. The mitochondrial dysfunction caused by U0126 or lacking WDPCP could be partially recovered by dexamethasone. The low expression of WDPCP in nasal epithelium could affect mitochondria via the MAPK/ERK pathway, which may contribute to the dysfunction in the beating of cilia in CRSwNP.
纤毛丧失和功能障碍是伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）的典型病理特征之一。含色氨酸-天冬氨酸（W-D）重复序列的平面细胞极性效应因子（WDPCP）已被证明是人类鼻上皮细胞纤毛发生的必需元件，但其在纤毛摆动中的作用仍不清楚。在本研究中，我们试图探究WDPCP的作用及其在鼻息肉组织纤毛摆动功能障碍背后的潜在机制。我们证实了WDPCP在鼻息肉上皮中的表达。我们还在原代人鼻窦上皮细胞中研究了丝裂原活化蛋白激酶/细胞外信号调节激酶（MAPK/ERK）通路，以探索WDPCP的功能。气液界面培养系统被用作模型，以验证WDPCP和MAPK/ERK通路在纤毛摆动中的作用。随着纤毛摆动功能障碍，我们观察到鼻息肉组织上皮中WDPCP表达降低。在本研究中，我们发现WDPCP对人鼻窦上皮细胞的线粒体生物合成和线粒体功能至关重要，这可能是由于MAPK/ERK通路的激活。由U0126或缺乏WDPCP引起的线粒体功能障碍可被地塞米松部分恢复。鼻上皮中WDPCP的低表达可能通过MAPK/ERK通路影响线粒体，这可能导致CRSwNP中纤毛摆动功能障碍。
