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Correlation of apical fluid-regulating channel proteins with lung function in human COPD lungs.

Zhao R, Liang X, Zhao M, Liu SL, Huang Y, Idell S, Li X, Ji HL - PLoS ONE (2014)

Bottom Line: The expression level of CFTR proteins was associated with FEV1 positively.Abundance of AQP5 proteins and extracellular superoxide dismutase (SOD3) was decreased and correlated with spirometry test results and gas exchange positively.Furthermore, these channel proteins were significantly associated with severity of disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America; Texas Lung Injury Institute, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.

ABSTRACT
Links between epithelial ion channels and chronic obstructive pulmonary diseases (COPD) are emerging through animal model and in vitro studies. However, clinical correlations between fluid-regulating channel proteins and lung function in COPD remain to be elucidated. To quantitatively measure epithelial sodium channels (ENaC), cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporin 5 (AQP5) proteins in human COPD lungs and to analyze the correlation with declining lung function, quantitative western blots were used. Spearman tests were performed to identify correlations between channel proteins and lung function. The expression of α and β ENaC subunits was augmented and inversely associated with lung function. In contrast, both total and alveolar type I (ATI) and II (ATII)-specific CFTR proteins were reduced. The expression level of CFTR proteins was associated with FEV1 positively. Abundance of AQP5 proteins and extracellular superoxide dismutase (SOD3) was decreased and correlated with spirometry test results and gas exchange positively. Furthermore, these channel proteins were significantly associated with severity of disease. Our study demonstrates that expression of ENaC, AQP5, and CFTR proteins in human COPD lungs is quantitatively associated with lung function and severity of COPD. These apically located fluid-regulating channels may thereby serve as biomarkers and potent druggable targets of COPD.

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Association of spirometry and expression of SOD3 and ENaC in COPD lungs.A. Total SOD3 and perdlco. B. α ENaC in ATII cells and spirometry. C. α ENaC expressed in ATI cells and fev1pd1a. D. β ENaC in ATI cells and lung function test. E. Total γ ENaC level and fev1prd1.
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pone-0109725-g004: Association of spirometry and expression of SOD3 and ENaC in COPD lungs.A. Total SOD3 and perdlco. B. α ENaC in ATII cells and spirometry. C. α ENaC expressed in ATI cells and fev1pd1a. D. β ENaC in ATI cells and lung function test. E. Total γ ENaC level and fev1prd1.

Mentions: Given the protective effects of SOD3 against COPD pathogenesis, and the association of SOD3 with FEV1 [26], [28], association between total SOD3 expression and lung function test was analyzed (Figure 4A). SOD3 expression level was related to perdlco, carbon monoxide diffusion capacity. Decreased value of perdlco in COPD may be due to large residual air stuck in the lungs and limited effective alveolar area.


Correlation of apical fluid-regulating channel proteins with lung function in human COPD lungs.

Zhao R, Liang X, Zhao M, Liu SL, Huang Y, Idell S, Li X, Ji HL - PLoS ONE (2014)

Association of spirometry and expression of SOD3 and ENaC in COPD lungs.A. Total SOD3 and perdlco. B. α ENaC in ATII cells and spirometry. C. α ENaC expressed in ATI cells and fev1pd1a. D. β ENaC in ATI cells and lung function test. E. Total γ ENaC level and fev1prd1.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4201481&req=5

pone-0109725-g004: Association of spirometry and expression of SOD3 and ENaC in COPD lungs.A. Total SOD3 and perdlco. B. α ENaC in ATII cells and spirometry. C. α ENaC expressed in ATI cells and fev1pd1a. D. β ENaC in ATI cells and lung function test. E. Total γ ENaC level and fev1prd1.
Mentions: Given the protective effects of SOD3 against COPD pathogenesis, and the association of SOD3 with FEV1 [26], [28], association between total SOD3 expression and lung function test was analyzed (Figure 4A). SOD3 expression level was related to perdlco, carbon monoxide diffusion capacity. Decreased value of perdlco in COPD may be due to large residual air stuck in the lungs and limited effective alveolar area.

Bottom Line: The expression level of CFTR proteins was associated with FEV1 positively.Abundance of AQP5 proteins and extracellular superoxide dismutase (SOD3) was decreased and correlated with spirometry test results and gas exchange positively.Furthermore, these channel proteins were significantly associated with severity of disease.

View Article: PubMed Central - PubMed

Affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America; Texas Lung Injury Institute, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.

ABSTRACT
Links between epithelial ion channels and chronic obstructive pulmonary diseases (COPD) are emerging through animal model and in vitro studies. However, clinical correlations between fluid-regulating channel proteins and lung function in COPD remain to be elucidated. To quantitatively measure epithelial sodium channels (ENaC), cystic fibrosis transmembrane conductance regulator (CFTR), and aquaporin 5 (AQP5) proteins in human COPD lungs and to analyze the correlation with declining lung function, quantitative western blots were used. Spearman tests were performed to identify correlations between channel proteins and lung function. The expression of α and β ENaC subunits was augmented and inversely associated with lung function. In contrast, both total and alveolar type I (ATI) and II (ATII)-specific CFTR proteins were reduced. The expression level of CFTR proteins was associated with FEV1 positively. Abundance of AQP5 proteins and extracellular superoxide dismutase (SOD3) was decreased and correlated with spirometry test results and gas exchange positively. Furthermore, these channel proteins were significantly associated with severity of disease. Our study demonstrates that expression of ENaC, AQP5, and CFTR proteins in human COPD lungs is quantitatively associated with lung function and severity of COPD. These apically located fluid-regulating channels may thereby serve as biomarkers and potent druggable targets of COPD.

Show MeSH
Related in: MedlinePlus