An Integrated Analysis of Radial Spoke Head and Outer Dynein Arm Protein Defects and Ciliogenesis Abnormality in Nasal Polyps
An Integrated Analysis of Radial Spoke Head and Outer Dynein Arm Protein Defects and Ciliogenesis Abnormality in Nasal Polyps
复制标题
鼻息肉径向辐条头和外动力臂蛋白缺陷及纤毛发生异常的综合分析
DOI：
10.3389/fgene.2019.01083
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发表时间：
2019
影响因子：
3.7
通讯作者：
Wang DY
中科院分区：
文献类型：
--
作者：
Zi XX;Guan WJ;Peng Y;Tan KS;Liu J;He TT;Ong YK;Thong M;Shi L;Wang DY
背景：鼻息肉（NP）是一种慢性上呼吸道炎症性疾病，通常由宿主防御缺陷引起。然而，屏障功能受损的机制，如纤毛介导的粘膜纤毛清除，仍然知之甚少。目的：探讨NP患者纤毛超微结构和纤毛发生标志物的表达及纤毛细胞表型。方法：97例NP患者及32例健康对照下鼻甲活检标本。免疫荧光染色、定量聚合酶链反应、单细胞自旋染色。我们对径向辐头蛋白（RSPH） 1、4A （RSPH4A）、9 （RSPH9）和动力蛋白轴突重链5 （DNAH5）定位模式进行了分类。建立了半定量评分系统来评估它们的表达模式及其与毛毛发生标志物[中心体蛋白110 （CP110）和叉头盒j1 (FOXJ1)]的关联。结果：NP患者RSPH1、RSPH4A、RSPH9和DNAH5的中位评分显著高于健康对照组，尤其是嗜酸性NP患者。两组RSPH1、RSPH4A、RSPH9、DNAH5的表达模式评分均呈正相关。在原代细胞标本中，异常表达模式在NP中更为常见。CP110和FOXJ1的总荧光强度在NPs中显著升高，并与RSPH1、RSPH4A、RSPH9、DNAH5的表达模式评分呈正相关。在NP中观察到纤毛延长的趋势。结论：在慢性气道炎症环境下，NP（特别是嗜酸性NP）纤毛超微结构标志物（即DNAH5）的异常表达与纤毛发生上调有关。
Background: Nasal polyp (NP) is a chronic upper airway inflammatory disease that is frequently triggered by defective host-defense. However, the mechanisms underlying the impaired barrier function such as cilia-mediated mucociliary clearance remain poorly understood. Objective: To assess ciliary ultrastructural and ciliogenesis marker expression and the phenotypes of ciliated cells in NP. Methods: NP biopsy samples were obtained from 97 NP patients and inferior turbinate from 32 healthy controls. Immunofluorescence staining, quantitative polymerase chain reaction, and single-cell cytospin staining were performed. We classified the patterns of radial spoke head protein (RSPH) 1, 4A (RSPH4A), 9 (RSPH9), and dynein axonemal heavy chain 5 (DNAH5) localization. A semi-quantitative scoring system was developed to assess their expression patterns and associations with ciliogenesis markers [centrosomal protein 110 (CP110) and forkhead box j1 (FOXJ1)]. Results: Median scores of RSPH1, RSPH4A, RSPH9, and DNAH5 were significantly higher in NP than in healthy controls, particularly in eosinophilic NPs. Expression pattern scores of RSPH1, RSPH4A, RSPH9, and DNAH5 correlated positively with each other in both groups. In primary-cell specimens, abnormal expression patterns were significantly more common in NP. The total fluorescence intensity of CP110 and FOXJ1 was significantly higher in NPs and correlated positively with expression pattern scores of RSPH1, RSPH4A, RSPH9, and DNAH5. A trend towards lengthened cilia was observed in NP. Conclusion: In the chronic airway inflammatory milieu, the up-regulated ciliogenesis correlates with the abnormal expression of ciliary ultrastructural markers (i.e., DNAH5) in NP (particularly eosinophilic NP).