Identification of pendrin as a common mediator for mucus production in bronchial asthma and chronic obstructive pulmonary disease.
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.
Nakao
Isao
I
Department of Biomolecular Sciences, Saga Medical School, Saga, Japan.
Kanaji
Sachiko
S
Ohta
Shoichiro
S
Matsushita
Hidetomo
H
Arima
Kazuhiko
K
Yuyama
Noriko
N
Yamaya
Mutsuo
M
Nakayama
Katsutoshi
K
Kubo
Hiroshi
H
Watanabe
Mika
M
Sagara
Hironori
H
Sugiyama
Kumiya
K
Tanaka
Hiroyuki
H
Toda
Shuji
S
Hayashi
Hiroaki
H
Inoue
Hiromasa
H
Hoshino
Tomoaki
T
Shiraki
Aya
A
Inoue
Makoto
M
Suzuki
Koichi
K
Aizawa
Hisamichi
H
Okinami
Satoshi
S
Nagai
Hiroichi
H
Hasegawa
Mamoru
M
Fukuda
Takeshi
T
Green
Eric D
ED
Izuhara
Kenji
K
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
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