title: Correlation of apical fluid-regulating channel proteins with lung function in human COPD lungs.
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.
authors.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.
authors.forename: Runzhen
authors.initials: R
authors.lastname: Zhao
authors.affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors.forename: Xinrong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America.
authors.forename: Meimi
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Molecular Microbiology and Immunology, Bond Life Sciences Center, University of Missouri, Columbia, Missouri, United States of America.
authors.forename: Shan-Lu
authors.initials: SL
authors.lastname: Liu
authors.affiliation: Department of Obstetrics and Gynecology, St. Joseph's Hospital and Medical Center, Phoenix, Arizona, United States of America.
authors.forename: Yao
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Department of Cellular and Molecular Biology, University of Texas Health Science Center at Tyler, Tyler, Texas, United States of America; Medicine, 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.
authors.forename: Steven
authors.initials: S
authors.lastname: Idell
authors.affiliation: Xinxiang Medical University, Xinxiang, Henan, China.
authors.forename: Xiumin
authors.initials: X
authors.lastname: Li
authors.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.
authors.forename: Hong-Long
authors.initials: HL
authors.lastname: Ji
mesh_terms: D000368:Aged; D051402:Aquaporin 5 / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D053503:Epithelial Sodium Channels / Q000235:genetics / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism* / Q000503:physiopathology; D011659:Pulmonary Gas Exchange
chemical_list: C496036:AQP5 protein, human; D051402:Aquaporin 5; C505032:CFTR protein, human; D053503:Epithelial Sodium Channels; D019005:Cystic Fibrosis Transmembrane Conductance Regulator