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...
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ndltd-LACETR-oai-collectionscanada.gc.ca-BVAU.2429-40722014-03-26T03:35:46Z Expression of beta subunit of epithelium sodium channel and cystic fibrosis transmembrane regulator in small airways obstruction in chronic obstructive pulmonary disease Chan, Becky Ka Man ENaC CFTR Mucin expression COPD 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. 2009-02-02T17:55:28Z 2009-02-02T17:55:28Z 2008 2009-02-02T17:55:28Z 2008-11 Electronic Thesis or Dissertation http://hdl.handle.net/2429/4072 eng University of British Columbia |
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language |
English |
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topic |
ENaC CFTR Mucin expression COPD |
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ENaC CFTR Mucin expression COPD Chan, Becky Ka Man Expression of beta subunit of epithelium sodium channel and cystic fibrosis transmembrane regulator in small airways obstruction in chronic obstructive pulmonary disease |
description |
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. |
author |
Chan, Becky Ka Man |
author_facet |
Chan, Becky Ka Man |
author_sort |
Chan, Becky Ka Man |
title |
Expression of beta subunit of epithelium sodium channel and cystic fibrosis transmembrane regulator in small airways obstruction in chronic obstructive pulmonary disease |
title_short |
Expression of beta subunit of epithelium sodium channel and cystic fibrosis transmembrane regulator in small airways obstruction in chronic obstructive pulmonary disease |
title_full |
Expression of beta subunit of epithelium sodium channel and cystic fibrosis transmembrane regulator in small airways obstruction in chronic obstructive pulmonary disease |
title_fullStr |
Expression of beta subunit of epithelium sodium channel and cystic fibrosis transmembrane regulator in small airways obstruction in chronic obstructive pulmonary disease |
title_full_unstemmed |
Expression of beta subunit of epithelium sodium channel and cystic fibrosis transmembrane regulator in small airways obstruction in chronic obstructive pulmonary disease |
title_sort |
expression of beta subunit of epithelium sodium channel and cystic fibrosis transmembrane regulator in small airways obstruction in chronic obstructive pulmonary disease |
publisher |
University of British Columbia |
publishDate |
2009 |
url |
http://hdl.handle.net/2429/4072 |
work_keys_str_mv |
AT chanbeckykaman expressionofbetasubunitofepitheliumsodiumchannelandcysticfibrosistransmembraneregulatorinsmallairwaysobstructioninchronicobstructivepulmonarydisease |
_version_ |
1716655290419511296 |