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鼻息肉中放射辐条头部和外动力蛋白臂蛋白缺陷与纤毛发生异常的综合分析

An Integrated Analysis of Radial Spoke Head and Outer Dynein Arm Protein Defects and Ciliogenesis Abnormality in Nasal Polyps.

作者信息

Zi Xiao-Xue, Guan Wei-Jie, Peng Yang, Tan Kai Sen, Liu Jing, He Ting-Ting, Ong Yew-Kwang, Thong Mark, Shi Li, Wang De-Yun

机构信息

Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan, China.

Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

出版信息

Front Genet. 2019 Nov 13;10:1083. doi: 10.3389/fgene.2019.01083. eCollection 2019.

Abstract

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. To assess ciliary ultrastructural and ciliogenesis marker expression and the phenotypes of ciliated cells in NP. 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 () 1, 4A (), 9 (), and dynein axonemal heavy chain 5 () localization. A semi-quantitative scoring system was developed to assess their expression patterns and associations with ciliogenesis markers [centrosomal protein 110 () and forkhead box j1 ()]. Median scores of , , and were significantly higher in NP than in healthy controls, particularly in eosinophilic NPs. Expression pattern scores of , , and 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 and was significantly higher in NPs and correlated positively with expression pattern scores of , , and . A trend towards lengthened cilia was observed in NP. In the chronic airway inflammatory milieu, the up-regulated ciliogenesis correlates with the abnormal expression of ciliary ultrastructural markers (i.e., ) in NP (particularly eosinophilic NP).

摘要

鼻息肉(NP)是一种慢性上呼吸道炎症性疾病,常由宿主防御缺陷引发。然而,诸如纤毛介导的黏液纤毛清除等屏障功能受损的潜在机制仍知之甚少。为了评估NP中纤毛超微结构、纤毛发生标志物表达以及纤毛细胞的表型。从97例NP患者中获取NP活检样本,并从32例健康对照中获取下鼻甲样本。进行了免疫荧光染色、定量聚合酶链反应和单细胞甩片染色。我们对辐条头蛋白1、4A、9和动力蛋白轴丝重链5的定位模式进行了分类。开发了一种半定量评分系统来评估它们的表达模式以及与纤毛发生标志物(中心体蛋白110和叉头框j1)的关联。NP中、、和的中位评分显著高于健康对照,尤其是在嗜酸性NP中。在两组中,、、和的表达模式评分彼此呈正相关。在原代细胞标本中,异常表达模式在NP中明显更常见。NP中及的总荧光强度显著更高,且与、、和的表达模式评分呈正相关。在NP中观察到纤毛有变长的趋势。在慢性气道炎症环境中,NP(尤其是嗜酸性NP)中纤毛发生上调与纤毛超微结构标志物(即)的异常表达相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d117/6863926/a29ed0fbaaad/fgene-10-01083-g001.jpg

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