WDPCP regulates the ciliogenesis of human sinonasal epithelial cells in chronic rhinosinusitis
WDPCP regulates the ciliogenesis of human sinonasal epithelial cells in chronic rhinosinusitis
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WDPCP 调节慢性鼻窦炎中人鼻窦上皮细胞的纤毛发生
DOI：
10.1002/cm.21351
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发表时间：
2017-02-01
期刊：
影响因子：
2.9
通讯作者：
Shi, Jianbo
中科院分区：
文献类型：
--
作者：
Ma, Yun;Sun, Yueqi;Shi, Jianbo
粘膜纤毛清除系统的损伤是慢性鼻窦炎发病机制的一个典型变化。然而，纤毛丢失的机制尚不清楚。WDPCP是纤毛发生所必需的关键蛋白，也是平面细胞极性信号系统的一个效应体。在这项研究中，我们试图确定WDPCP在慢性鼻窦炎患者纤毛丢失中的作用。我们证实了WDPCP在慢性鼻窦炎患者和对照组的人鼻窦上皮中的表达。我们还采用气液界面培养人鼻窦上皮细胞体外模型，研究WDPCP的功能。然后我们探讨了鼻窦炎、WDPCP和炎症之间的联系。慢性鼻窦炎患者鼻窦上皮WDPCP的表达与对照组相比显著降低，同时伴有纤毛缺失。体外实验发现WDPCP水平先升高后降低。抑制WDPCP的表达可导致纤毛数量和长度减少，并导致Septin7的表达减少。Th1型炎症介质可降低WDPCP的表达。综上所述，炎症因子导致WDPCP表达降低，从而导致人鼻窦炎纤毛发育受损。
Damage to the mucociliary clearance system is a typical change in the pathogenesis in chronic rhinosinusitis. However, the mechanisms underlying cilia loss remain unclear. WDPCP is a key protein essential for ciliogenesis, and is also an effector of the planar cell polarity signaling system. In this study, we sought to determine the role of WDPCP in cilia loss in patients with chronic rhinosinusitis. We demonstrated the expression of WDPCP in human sinonasal epithelium from patients with chronic rhinosinusitis and control subjects. We also used air‐liquid interface to culture primary human sinonasal epithelial cells in‐vitro model and to investigate WDPCP function. We then explored links between rhinosinusitis, WDPCP and inflammation. Accompanied with cilia loss, expression of WDPCP in human sinonasal epithelium from patients with chronic rhinosinusitis was decreased significantly compared with control subjects. In vitro study, we found that WDPCP level increased at first, and then decreased. Inhibiting WDPCP expression could lead to the poor quantity and length of cilia with reduced expression of Septin7. Also, Th1 type inflammatory mediators could decrease the expression of WDPCP. In conclusion, inflammatory cytokines cause reduced WDPCP expression, which contributes to impaired ciliogenesis in human rhinosinusitis.