Correlation of Bromodomain Protein BRD4 Expression With Epithelial-Mesenchymal Transition and Disease Severity in Chronic Rhinosinusitis With Nasal Polyps.

Zhaoyang Cui,Fengyang Xie,Zhiyong Yue,Xuanchen Zhou,Ling Ding,Shuai Xu,Hong Zhang,Jie Han,Yiqing Liu

doi:10.3389/fmed.2020.00413

Abstract

Objectives: This study aimed to explore the relationship between bromodomain-containing protein 4 (BRD4), epithelial–mesenchymal transition (EMT), and disease severity in chronic rhinosinusitis with nasal polyps (CRSwNP).Methods: We performed immunofluorescent (IF) staining to evaluate the expression of BRD4 in the polyp tissues of CRSwNP and inferior turbinate mucosa of healthy controls. The relationship between BRD4 and EMT was evaluated by the BRD inhibitor JQ1 and BRD4 siRNA in primary human nasal polyp–derived epithelial cells. Disease severity was scored by using the Lund–Mackay scores of paranasal sinus computed tomography (CT) scans.Results: The expression of BRD4 in patients with CRSwNP was significantly higher than that in healthy controls. The loss of BRD4 function by the BRD inhibitor JQ1 and BRD4 siRNA resulted in the reduction of E-cadherin, increasing vimentin, and Snai1 mRNA expression. Moreover, the expression of BRD4 was related to the total CT scan scores (r = 0.4682, P = 0.0210).Conclusions: BRD4 had higher expression in CRSwNP than in healthy controls and might be associated with EMT in CRSwNP. BRD4 mRNA expression was associated with disease severity in CRSwNP.

Highlights

Chronic rhinosinusitis (CRS) is highly prevalent, influencing ∼ 11–15% of the adult people [1, 2], and contributing to direct health care costs of $11 billion each year in the European area [3]
We evaluated the expression of Bromodomain-containing protein 4 (BRD4) in human nasal polyps (NP) tissues of CRS with nasal polyps (CRSwNP) and healthy controls at the mRNA and tissue levels and analyzed the correlation between BRD4 expression and CRSwNP disease severity
In order to evaluate whether BRD4 was altered in NP tissues from patients with CRSwNP, we determined the mRNA expression of BRD4

Summary

Introduction

Chronic rhinosinusitis (CRS) is highly prevalent, influencing ∼ 11–15% of the adult people [1, 2], and contributing to direct health care costs of $11 billion each year in the European area [3]. Chronic rhinosinusitis refers to a heterogeneous group of diseases with common symptoms and clinical findings, but different pathophysiologies. It has been divided into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps basing on whether nasal polyps are present or absent [4]. CRSwNP is a chronic inflammatory disease characterized by the inflammation of the nasal mucosa, nasal obstruction, and the growth of nasal polyps (NP) [3]. The pathogenesis of CRSwNP that is related to TH2-based inflammation has been shown in some published literatures [7,8,9]. The evidence shown above demonstrates that the inflammation mainly contributes to the pathogenic process of CRSwNP

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