Aberrant localization of FOXJ1 correlates with the disease severity and comorbidities in patients with nasal polyps

Yang Peng,Zhaoni Wang,Zhenchao Zhu,Qianhui Qiu,Xiaoxue Zi,Mark Thong,Kai Sen Tan,Qintai Yang,De-Yun Wang,Tengfei Tian,Yew Kwang Ong,Haiyu Hong,Zhuo Chen,Li Shi,Wei-Jie Guan

doi:10.1186/s13223-018-0296-z

Abstract

BackgroundUpper airway inflammatory diseases are associated with abnormal expression of nasal epithelial forkhead-box J1 (FOXJ1) which regulates motile cilia formation. We sought to investigate whether aberrant FOXJ1 localizations correlate with the disease severity and the co-existence of allergic rhinitis (AR) or asthma in patients with nasal polyps (NPs).MethodsWe elucidated localization patterns of FOXJ1 by performing immunofluorescence assays in nasal specimens and cytospin samples from controls and patients with NPs. We also assayed mRNA expression levels of FOXJ1 by using quantitative real-time polymerase chain reaction. Four localization patterns [normal (N), intermediate (I), mislocalization (M), and absence (A)] were defined. A semi-quantitative scoring system was applied for demonstrating FOXJ1 localization in five areas per paraffin section, with individual sections being scored between 0 and 2.ResultsFOXJ1 localization score was significantly higher in samples from NPs than in controls (P < 0.001). Elevated FOXJ1 localization scores and down-regulation of FOXJ1 mRNA levels were observed in NPs with co-existing AR or asthma (all P < 0.05). Moreover, FOXJ1 localization scores positively correlated with Lund–Mackay score (r = 0.362, P = 0.007). Of primary cytospin samples, the mean percentage of patients with FOXJ1 localization patterns N, I, M and A was 15.0%, 3.3%, 53.3% and 28.3% in NPs, and 82.5%, 5.0%, 5.0% and 7.5% in controls, respectively (P < 0.001).ConclusionsAberrant localization of FOXJ1 correlates with the severity and co-existence of AR or asthma in patients with NPs, and might be a novel target for assessment and intervention in NPs.

Highlights

Upper airway inflammatory diseases are associated with abnormal expression of nasal epithelial forkhead-box J1 (FOXJ1) which regulates motile cilia formation
CRS with NP (CRSwNP) diagnoses were made according to the European Position Paper on Rhinosinusitis and Nasal Polyps 2012 [3], and allergic rhinitis (AR) was diagnosed according to Allergic Rhinitis and its Impact on Asthma (ARIA) [12] based on the clinical symptoms combined with skin prick test (Dermatophagoides farinae, Dermatophagoides pteronyssinus, pollens of oak, ragweed, mugwort, Humulus japonicus, cat and dog dander allergens) (Allergopharma, Reinbek, Germany) or serum total/specific IgE detected by using AllergyScreen® (Mediwiss Analytic GmbH, Moers, Germany)
Increased aberrant localization of FOXJ1 in nasal polyp (NP) We initially examined the localization patterns of FOXJ1 in nasal epithelial cilia by performing IF staining of samples from control subjects and patients with NPs

Summary

Introduction

Upper airway inflammatory diseases are associated with abnormal expression of nasal epithelial forkhead-box J1 (FOXJ1) which regulates motile cilia formation. We sought to investigate whether aberrant FOXJ1 localizations correlate with the disease severity and the co-existence of allergic rhinitis (AR) or asthma in patients with nasal polyps (NPs). The correlation between ciliary impairment and the severity of NPs remains unclear. It is unknown whether common comorbidities of NPs such as allergic rhinitis (AR) and asthma, in which impaired ciliary function is implicated, would further aggravate the impairment of ciliary function in NPs [3,4,5]. Elucidation of the pathogenic factors underlying NP formation (i.e. impaired mucociliary clearance) may facilitate better clinical management via early diagnosis and intervention

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