title: Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease.
abstract: Excessive production of airway mucus is a cardinal feature of bronchial asthma and chronic obstructive pulmonary disease (COPD) and contributes to morbidity and mortality in these diseases. IL-13, a Th2-type cytokine, is a central mediator in the pathogenesis of bronchial asthma, including mucus overproduction. Using a genome-wide search for genes induced in airway epithelial cells in response to IL-13, we identified pendrin encoded by the SLC26A4 (PDS) gene as a molecule responsible for airway mucus production. In both asthma and COPD mouse models, pendrin was up-regulated at the apical side of airway epithelial cells in association with mucus overproduction. Pendrin induced expression of MUC5AC, a major product of mucus in asthma and COPD, in airway epithelial cells. Finally, the enforced expression of pendrin in airway epithelial cells in vivo, using a Sendai virus vector, rapidly induced mucus overproduction in the lumens of the lungs together with neutrophilic infiltration in mice. These findings collectively suggest that pendrin can induce mucus production in airway epithelial cells and may be a therapeutic target candidate for bronchial asthma and COPD.
authors.affiliation: Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Nakao
authors.forename: Sachiko
authors.initials: S
authors.lastname: Kanaji
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ohta
authors.forename: Hidetomo
authors.initials: H
authors.lastname: Matsushita
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Arima
authors.forename: Noriko
authors.initials: N
authors.lastname: Yuyama
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Nakayama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo
authors.forename: Mika
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hironori
authors.initials: H
authors.lastname: Sagara
authors.forename: Kumiya
authors.initials: K
authors.lastname: Sugiyama
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Shuji
authors.initials: S
authors.lastname: Toda
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Hayashi
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Aya
authors.initials: A
authors.lastname: Shiraki
authors.forename: Makoto
authors.initials: M
authors.lastname: Inoue
authors.forename: Koichi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Aizawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Okinami
authors.forename: Hiroichi
authors.initials: H
authors.lastname: Nagai
authors.forename: Mamoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukuda
authors.forename: Eric D
authors.initials: ED
authors.lastname: Green
authors.forename: Kenji
authors.initials: K
authors.lastname: Izuhara
mesh_terms: D000368:Aged; D000818:Animals; D001249:Asthma / Q000235:genetics / Q000276:immunology*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000276:immunology; D005260:Female; D015894:Genome, Human / Q000276:immunology; D006801:Humans; D018793:Interleukin-13 / Q000276:immunology; D008168:Lung / Q000276:immunology; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008875:Middle Aged; D055271:Mucin 5AC; D009077:Mucins / Q000235:genetics / Q000276:immunology*; D009093:Mucus / Q000276:immunology*; D020556:Neutrophil Infiltration / Q000235:genetics / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology*; D000076988:Sulfate Transporters; D018418:Th2 Cells / Q000276:immunology
chemical_list: D018793:Interleukin-13; C524678:MUC5AC protein, human; D026901:Membrane Transport Proteins; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D009077:Mucins; C085609:SLC26A4 protein, human; D000076988:Sulfate Transporters