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

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.

Effects of glucocorticoid on the expression and regulation of aquaporin 5 in the paranasal sinus of rats with chronic rhinosinusitis

“…This distribution is consistent with previous findings in humans (14,24). The subepithelial glandular cells are established to participate in mucus secretion and consistency, which maintain the function of the mucociliary system.…”

Staphylococcus Aureus V8 protease disrupts the integrity of the airway epithelial barrier and impairs IL‐6 production in vitro

“…Nasal polyp biopsy specimens showed decreased expression of TJ proteins, which also negatively correlated with disease severity and eosinophilic inflammation. It has been suggested that CRS barrier dysfunction is a result of environmental, microbial, and host factors . Previous research from our group has shown that the supernatants from S. aureus ATCC strain 13565 disrupt the TJs of HNEC‐ALI cultures; however, the identity of the toxin(s) responsible for this effect has yet to be identified .…”

“…It has been suggested that CRS barrier dysfunction is a result of environmental, microbial, and host factors. 4,34,35 Previous research from our group has shown that the supernatants from S. aureus ATCC strain 13565 disrupt the TJs of HNEC-ALI cultures; however, the identity of the toxin(s) responsible for this effect has yet to be identified. 9 This study does not exclude other S. aureus products as the responsible factor but rather highlights the protease family for further investigation.…”

Etiology of epithelial barrier dysfunction in patients with type 2 inflammatory diseases

“…The group of Bachert reported that ZO-1, occludin and E-cadherin were all reduced in mature polyps removed from CRSwNP patients 51 . Moreover, aquaporin 5, a marker of epithelial differentiation, was significantly reduced in sinonasal samples of CRSwNP subjects compared to CRSsNP or controls 52 . Physical evidence of disruption of epithelial barrier in CRS includes prominent acanthosis and acantholysis 47 .…”