AUTHOR=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 

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

JOURNAL=Frontiers in Genetics

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2019.01083

DOI=10.3389/fgene.2019.01083

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> 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.</p><p><bold>Objective:</bold> To assess ciliary ultrastructural and ciliogenesis marker expression and the phenotypes of ciliated cells in NP.</p><p><bold>Methods:</bold> 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 (<italic>RSPH</italic>) 1, 4A (<italic>RSPH4A</italic>), 9 (<italic>RSPH9</italic>), and dynein axonemal heavy chain 5 (<italic>DNAH5</italic>) localization. A semi-quantitative scoring system was developed to assess their expression patterns and associations with ciliogenesis markers [centrosomal protein 110 (<italic>CP110</italic>) and forkhead box j1 (<italic>FOXJ1</italic>)].</p><p><bold>Results:</bold> Median scores of <italic>RSPH1</italic>, <italic>RSPH4A</italic>, <italic>RSPH9,</italic> and <italic>DNAH5</italic> were significantly higher in NP than in healthy controls, particularly in eosinophilic NPs. Expression pattern scores of <italic>RSPH1</italic>, <italic>RSPH4A</italic>, <italic>RSPH9,</italic> and <italic>DNAH5</italic> 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 <italic>CP110</italic> and <italic>FOXJ1</italic> was significantly higher in NPs and correlated positively with expression pattern scores of <italic>RSPH1</italic>, <italic>RSPH4A</italic>, <italic>RSPH9,</italic> and <italic>DNAH5</italic>. A trend towards lengthened cilia was observed in NP.</p><p><bold>Conclusion:</bold> In the chronic airway inflammatory milieu, the up-regulated ciliogenesis correlates with the abnormal expression of ciliary ultrastructural markers (i.e., <italic>DNAH5</italic>) in NP (particularly eosinophilic NP).</p>