Absence or mislocalization of DNAH5 is a characteristic marker for motile ciliary abnormality in nasal polyps

Abstract

NA. Laryngoscope, 128:E97-E104, 2018.

Downregulation and Aberrant Localization of Forkhead Box J1 in Allergic Nasal Mucosa

“…Recently, we have identified mislocalization and altered expression of DNAH5, the critical cilia structural protein, in patients with chronic rhinosinusitis with nasal polyps, suggesting their possible contribution to impaired mucociliary clearance [7]. In this study, we expanded our investigation to the assessment of FOXJ1, a critical ciliogenesis marker, to determine whether the altered expression or localization of FOXJ1 was associated with AR.…”

“…We referred to the criterion from Shoemark et al [17] and our previously published study [7]. That is, samples with more than 7 out of 10 ciliated cells (70%) clearly labeled with cilia markers would be considered normal.…”

“…For instance, the presence of dynein arms is indispensable to the proper formation of microtubule-based axoneme [11]. Sugier et al [12] and our study team [7] have consistently demonstrated that the abnormality of the dynein arm-related marker, dynein axonemal heavy chain 5 (DNAH5), might be implicated in chronic and allergic inflammation of the airway epithelium. However, no study has revealed whether the altered mRNA expression levels of dynein axonemal intermediate chain 1 (DNAI1), dynein axonemal light intermediate chain 1 (DNALI1), and DNAH9, which are regulated by FOXJ1 [13], are also present in the allergic nasal mucosa.…”

“…Normal nasal mucociliary clearance is essential to maintaining proper nasal epithelial host defense, and impaired mucociliary clearance has been a common cause of chronic airway diseases and may be implicated in the significant associations between AR and its comorbidities [4, 5]. In fact, abnormal expression or mislocalization of ciliary markers has been linked to defective host defenses of the epithelium that may be responsible for the pathogenesis of many chronic airway diseases [6, 7]. However, the molecular mechanisms underlying the impaired mucociliary clearance in allergic nasal mucosa remains unknown.…”

Respiratory Viral Infections in Exacerbation of Chronic Airway Inflammatory Diseases: Novel Mechanisms and Insights From the Upper Airway Epithelium

“…that aid in the proper function of the motile cilia in the airways are aberrantly expressed in ciliated airway epithelial cells which are the major target for RV infection (Griggs et al, 2017). Such form of secondary cilia dyskinesia appears to be present with chronic inflammations in the airway, but the exact mechanisms are still unknown (Peng et al, , 2019Qiu et al, 2018). Nevertheless, it was found that in viral infection such as IFV, there can be a change in the metabolism of the cells as well as alteration in the ciliary gene expression, mostly in the form of down-regulation of the genes such as dynein axonemal heavy chain 5 (DNAH5) and multiciliate differentiation And DNA synthesis associated cell cycle protein (MCIDAS) (Tan et al, 2018b.…”