title: Impairment of cilia architecture and ciliogenesis in hyperplastic nasal epithelium from nasal polyps.
abstract: BACKGROUND
  Aberrant airway epithelial remodeling is one of the cardinal histopathologic features of inflammatory airway diseases, but whether it alters the mucociliary apparatus remains unknown.
  
  
  OBJECTIVE
  We sought to investigate the morphologic pattern of motile cilia and ciliogenesis-associated makers in hyperplastic nasal epithelium from nasal polyps (NPs) both in vivo and in vitro.
  
  
  METHODS
  Biopsy specimens obtained from patients with NPs (n = 44) and inferior turbinate from healthy control subjects (n = 38) were analyzed by using scanning electron microscopy, immunofluorescence staining, single-cell (cytospin) staining, quantitative real-time PCR, and human nasal epithelial stem/progenitor cell culture and differentiation.
  
  
  RESULTS
  Abnormal cilia architecture (untidy, overly dense, and lengthened) was more commonly observed in patients with NPs by using scanning electron microscopy. Ectopic lengthened cilia were visualized by means of immunofluorescence (patients with NPs: 6.33 μm [5.51-7.43 μm] vs control subjects: 3.73 μm [3.50-4.27 μm], P < .0001), at the site of epithelial hyperplasia in isolated single cells (patients with NPs: 6.55 ± 0.23 μm vs control subjects 4.89 ± 0.24 μm, P < .0001), and in differentiated ciliated cells derived from human nasal epithelial stem/progenitor cells (patients with NPs: 9.20 ± 0.56 μm vs control subjects: 5.21 ± 0.37 μm, P < .0001). Ciliary beat frequency was found to be significantly slower in patients with NPs than control subjects in vitro. Both protein and mRNA levels of ciliogenesis-associated markers (centrosomal protein 110 [CP110], forkhead box J1 [Foxj1], and P73 isoform with an N-terminal transactivation domain [TAp73]) were significantly increased in patients with NPs versus those seen in control subjects and were positively correlated with cilia length.
  
  
  CONCLUSIONS
  For the first time, this study demonstrates for that motile cilia impairment is a co-condition of epithelial hyperplasia in patients with NPs, and this impairment of function is a likely cause of chronic mucosal inflammation or infection (eg, biofilm) observed in patients with chronic rhinosinusitis.
authors.affiliation: Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Ying Ying
authors.initials: YY
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Chun Wei
authors.initials: CW
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Siew Shuen
authors.initials: SS
authors.lastname: Chao
authors.affiliation: Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Feng Gang
authors.initials: FG
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, Qilu Hospital, Shandong University, Shandong, China.
authors.forename: Xue Min
authors.initials: XM
authors.lastname: Yu
authors.affiliation: Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Jing
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Biostatistics Unit, National University of Singapore, National University Health System, Singapore.
authors.forename: Liang
authors.initials: L
authors.lastname: Shen
authors.affiliation: Department of Medicine and Biological Chemistry, University of California, Irvine, Calif.
authors.forename: William
authors.initials: W
authors.lastname: Gordon
authors.affiliation: Department of Otolaryngology, Qilu Hospital, Shandong University, Shandong, China; Key Laboratory of Otorhinolaryngology, Ministry of Health, Shandong University, Shandong, China. Electronic address: shili126@sina.com.
authors.forename: Li
authors.initials: L
authors.lastname: Shi
authors.affiliation: Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: entwdy@nus.edu.sg.
authors.forename: De Yun
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000328:Adult; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D002923:Cilia / Q000473:pathology* / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006965:Hyperplasia; D008297:Male; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009297:Nasal Mucosa / Q000473:pathology*; D009298:Nasal Polyps / Q000473:pathology* / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C467559:CCP110 protein, human; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C106349:FOXJ1 protein, human; D051858:Forkhead Transcription Factors; D008869:Microtubule-Associated Proteins; D009687:Nuclear Proteins; D010750:Phosphoproteins; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
keywords: Impairments of cilia architecture; hyperplasia; nasal polyps