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Expression of beta subunit of epithelium sodium channel and cystic fibrosis transmembrane regulator in small airways obstruction in chronic obstructive pulmonary disease

Background: Excess plugging of small airways is associated with premature death in
chronic obstructive pulmonary disease (COPD). Over-expression of beta-epithelial sodium channel (β-ENaC) in airway epithelia in mice resulted in plugging of small airways while cystic fibrosis transmembrane regulator (CFTR) negatively regulated ENaC activity in cell models.
Purpose: To test the hypothesis that accumulation of mucus exudates observed with the progression of COPD is related to excess airway epithelial sodium re-absorption as a result of over-expression of β-ENaC and reduced expression of CFTR by small airway epithelia.
Methods: Small airway epithelial samples from frozen lungs from patients at different levels of COPD severity were isolated by laser capture microdissection (LCM). β-ENaC, CFTR, and β-actin (control) gene expression was determined by qRT-PCR and compared to
expression in entire airways and lung parenchyma surrounding these airways. β-ENaC
protein as well as epithelial mucin expression and mucus plugging were localized and
quantified after immunohistochemical and periodic acid Schiff staining, respectively.
Results: β-ENaC mRNA expression had a strong positive correlation with that of CFTR (p<O.0001) in airway epithelia and surrounding lung parenchyma (p=O.Ol) but not whole airways. β-ENaC mRNA and protein expression were positively correlated (p=O.4O, p=O.O5) and protein expression significantly increased with GOLD stage of COPD severity.
Epithelial mucin expression positively correlated with β-ENaC (p=O.38, p=O.O5) and CFTR (p=OAO, p=O.O4.) mRNA and with mucus plugging (p=O. 43 , ptO.OOO2). CFTR mRNA also correlated positively with mucus plugging (p=O. 48 , p=O.O2).
Conclusions: Strong positive correlations between β-ENaC and CFTR mRNA expression that are limited to the lung parenchyma and epithelium suggest a novel mechanism of mRNA regulation. This differs from their functional relationship where an inverse relationship between CFTR expression and β-ENaC activity has been reported. Positive correlations of epithelial mucin or mucus plugging with CFTR mRNA but not β-ENaC protein expression in the small airway epithelium suggest that CFTR may regulate mucin at this site independently of β-ENaC protein. The relationship between β-ENaC mRNA andepithelial mucin expression could be due to strong correlations between β-ENaC and CFTR mRNA expression but β-ENaC’s relationship with COPD GOLD stage suggests it may nevertheless play a role in COPD. / Medicine, Faculty of / Medicine, Department of / Experimental Medicine, Division of / Graduate

Identiferoai:union.ndltd.org:UBC/oai:circle.library.ubc.ca:2429/4072
Date11 1900
CreatorsChan, Becky Ka Man
PublisherUniversity of British Columbia
Source SetsUniversity of British Columbia
LanguageEnglish
Detected LanguageEnglish
TypeText, Thesis/Dissertation
Format4190219 bytes, application/pdf
RightsAttribution-NonCommercial-NoDerivatives 4.0 International, http://creativecommons.org/licenses/by-nc-nd/4.0/

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