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水通道蛋白 5 和上皮屏障蛋白在伴有和不伴有鼻息肉的慢性鼻-鼻窦炎中的黏膜表达。

Mucosal expression of aquaporin 5 and epithelial barrier proteins in chronic rhinosinusitis with and without nasal polyps.

机构信息

Director, Maryland Nose & Sinus Center Rhinology Fellowship Program and of the Department of Otolaryngology-Head and Neck Surgery, Union Memorial Hospital and Sinai Hospital, Baltimore, MD, USA; Department of Otolaryngology-Head and Neck Surgery, Union Memorial Hospital, Baltimore, MD, USA.

Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore.

出版信息

Am J Otolaryngol. 2014 May-Jun;35(3):377-83. doi: 10.1016/j.amjoto.2013.11.011. Epub 2013 Dec 7.

Abstract

OBJECTIVES

The purpose of this study is to characterize the association between altered epithelial barrier function, represented by changes in histology and differential expression of the mucosal water membrane permeability protein aquaporin 5 (AQP5), and the pathophysiology of chronic refractory sinusitis (CRS) in patients with and without nasal polyposis.

STUDY DESIGN

Prospective clinical study.

SETTING

Tertiary rhinology referral center.

PARTICIPANTS

Sinonasal samples were obtained from seven CRS subjects with nasal polyps (CRSwNP), seven CRS without nasal polyposis (CRSsNP), and five control healthy patients.

METHODS

Mucosal membrane changes were evaluated through hematoxylin and eosin staining of the membrane barrier and immunohistochemical staining of AQP5 expression, a membrane channel protein that affects trans-epithelial water permeability and tissue edema. AQP5 expression was confirmed by real-time PCR (rt-PCR) and western blot. Levels of other membrane proteins, including E-cadherin and Septin-2, were also assessed.

RESULTS

CRSwNP patients showed substantial histologic evidence of membrane remodeling with increased edema and glandular hyperplasia. The epithelial expression of AQP5 was significantly lower in CRSwNP as compared to CRSsNP or control. There was no significant difference in the expression of E-cadherin and Septin-2.

CONCLUSIONS

Collectively, these data suggest that the mucosal epithelial barrier is compromised in the context of CRS (predominantly in CRSwNP) when compared to control and that AQP5 acts as a key tight junction protein in the maintenance of mucosal water homeostasis. We hypothesize that AQP5 plays a possible role in the pathophysiology of mucosal edema and polyp formation.

摘要

目的

本研究旨在探讨改变上皮屏障功能(表现为组织学改变和黏膜水膜通透性蛋白水通道蛋白 5(AQP5)的差异表达)与伴有和不伴鼻息肉的慢性难治性鼻窦炎(CRS)病理生理学之间的关系。

研究设计

前瞻性临床研究。

设置

三级鼻科学转诊中心。

参与者

从 7 例伴有鼻息肉的 CRS 患者(CRSwNP)、7 例无鼻息肉的 CRS 患者(CRSsNP)和 5 例健康对照患者中获取鼻黏膜样本。

方法

通过对黏膜屏障进行苏木精和伊红染色以及对影响跨上皮水通透性和组织水肿的膜通道蛋白 AQP5 的免疫组织化学染色来评估黏膜膜变化。通过实时 PCR(rt-PCR)和 Western blot 证实 AQP5 表达。还评估了其他膜蛋白,包括 E-钙黏蛋白和 Septin-2 的水平。

结果

CRSwNP 患者表现出明显的膜重塑组织学证据,水肿和腺体增生增加。与 CRSsNP 或对照相比,CRSwNP 中 AQP5 的上皮表达明显降低。E-钙黏蛋白和 Septin-2 的表达没有显著差异。

结论

总的来说,这些数据表明,与对照相比,CRS(主要在 CRSwNP 中)时黏膜上皮屏障受损,AQP5 作为维持黏膜水动态平衡的关键紧密连接蛋白发挥作用。我们假设 AQP5 在黏膜水肿和息肉形成的病理生理学中可能发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0f0/5906045/8214709e7662/nihms959017f1.jpg

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