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

Abstract

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