Aquaporins: A channel to understanding the pathogenesis of Chronic Rhinosinusitis

Author: Claire Amelia Frauenfelder

Frauenfelder, Claire Amelia, 2015 Aquaporins: A channel to understanding the pathogenesis of Chronic Rhinosinusitis, Flinders University, School of Medicine

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Abstract

Aquaporins (AQPs) are cell membrane water transport channels and their discovery has revolutionised the understanding of water movement through tissue and tissue remodelling in the last 20 years. In chronic rhinosinusitis (CRS), there are pathological features suggestive of aberrant sinonasal water transport including altered composition of secretions, mucosal oedema, tissue remodelling and polyp formation. This project was undertaken to investigate a possible link between AQPs and CRS. Chronic rhinosinusitis (CRS) is a chronic, inflammatory condition of the nose and paranasal sinuses that affects up to 10% of the Australian population. Characterised by inflammation of the sinonasal mucosa, CRS was defined by the European Position Paper on Rhinosinusitis and Nasal Polyps 2012 (EPOS 2012) based on clinical symptoms and investigation findings. Chronic rhinosinusitis (CRS) is further classified phenotypically into CRS with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). However, AQP expression in normal and CRS sinus tissue remains incompletely understood. This study provides baseline knowledge of sinonasal mucosa AQP expression for the future investigation of AQPs in the pathogenesis of CRS. The hypothesis of this thesis was that AQP expression and location are altered in CRS in comparison to normal sinonasal mucosa. Methods Sinonasal tissue was collected during endoscopic sinus surgery or trans-sphenoidal surgery from three patient groups: normal controls, CRSwNP and CRSsNP. The mRNA expression of human AQP0-QP12b was determined using quantitative real-time PCR. Cellular localisation of AQP1, AQP3, AQP4, AQP5, AQP7 and AQP11 was determined by immunohistochemistry. Results The mRNA of AQP0-AQP11 was identified in all samples; however, AQP12b mRNA was not detected. Statistically significant differences in the mRNA expression levels of AQP4 and AQP11 were identified between normal and CRSwNP patients (p<0.05). Differences in the cellular localisation of AQPs were observed in both CRSsNP and CRSwNP patients vs. normal controls. More intense localisation to the cell cytoplasm was observed for AQP5 in glandular epithelium (CRSwNP; p<0.05) and surface epithelium (CRSsNP; p<0.05), and AQP4 in glandular epithelium (CRSsNP; p<0.05). Conclusion This study characterises normal human sinonasal AQP mRNA expression and protein localisation. The findings correlate well with the few published studies in this area, and extend the knowledge of AQP expression in human sinonasal tissue by providing normal baseline AQP expression profiles for future reference. Increased intracellular localisation of AQP4 and AQP5 was identified in both phenotypes of CRS, raising interesting questions regarding the significance of these findings in CRS aetiology. Future work will focus on the implication of intracellular AQPs on water flow and/or tissue remodelling in CRS.

Keywords: Aquaporin,nose,sinus,sinonasal,mucosa,sinusitis,rhinosinusitis,chronic,human,polyps
Subject: Medicine thesis

Thesis type: Masters
Completed: 2015
School: School of Medicine
Supervisor: Professor A. Simon Carney