Decreased expression of human aquaporin-5 correlated with mucus overproduction in airways of chronic obstructive pulmonary disease.
OBJECTIVE
To investigate the relationship between aquaporin-5 (AQP5) expression and mucus overproduction in the airways of Chinese patients with chronic obstructive pulmonary disease (COPD) and the correlation with pulmonary function change.


METHODS
Bronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to July 2004. Twenty-five patients were diagnosed as COPD patients, and another 20 were diagnosed as the control patients. The expressions of AQP5, mucin 5AC (MUC5AC), and mucin in bronchial tissues were detected by semiquantitative RT-PCR, in situ hybridization, and immunohistochemical and alcian blue-periodic acid-Schiff (AB-PAS) staining, respectively.


RESULTS
Compared with the control group, an attenuated expression of AQP5 was detected throughout the bronchial tissues from patients with COPD (P<0.01), but no difference existed in the lung tissues (P>0.05). Simultaneously, increased staining of MUC5AC and mucus in submucosal glands were noted (P<0.01, respectively). Smoking attenuated the expressions of AQP5 and increased the staining of MUC5AC and mucus in submucosal glands in the COPD groups (P<0.01), while there were no significant differences observed in the control group (P>0.05). The decreased expression of AQP5 mRNA was correlated with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) (r=0.60, P<0.01), FEV1% predicted value (r=0.60, P<0.01), maximal expiratory flow in 50% vital capacity (V50) % predicted value (r=0.55, P<0.01), and maximal expiratory flow in 25% vital capacity (V25) % predicted value (r=0.45, P<0.01). The decreased expression was negatively correlated with MUC5AC mRNA of the epithelium airways (r=-0.45, P<0.01) and the AB-PAS-stained area of submucosal glands (r=-0.61, P<0.01). The upregulation of MUC5AC mRNA correlated with the positively AB-PAS-stained area of submucosal glands and correlated negatively with FEV1/FVC (r=-0.53; P<0.01), FEV1% predicted value (r=-0.53; P<0.01), V50% predicted value (r=-0.48; P<0.01), and V25% predicted value (r=-0.43; P<0.01).


CONCLUSIONS
The attenuated gene expression of AQP5 existed in the airways of Chinese COPD patients, which was complicated by mucus hypersecretion. The decreased expression of AQP5 mRNA may be related to the severity of airflow obstruction.
Wang
Ke
K
Division of Pulmonary Diseases, State Key Laboratory of Biotherapy of China, and Department of Respiratory Medicine, West China Hospital of Sichuan University, Sichuan, China.
Feng
Yu-lin
YL
Wen
Fu-qiang
FQ
Chen
Xue-rong
XR
Ou
Xue-mei
XM
Xu
Dan
D
Yang
Jie
J
Deng
Zhi-ping
ZP
D051402:Aquaporin 5 / Q000032:analysis / Q000235:genetics*; D001980:Bronchi / Q000378:metabolism*; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D055271:Mucin 5AC; D009077:Mucins / Q000032:analysis / Q000235:genetics*; D009093:Mucus / Q000378:metabolism*; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis
D051402:Aquaporin 5; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D009077:Mucins; D012333:RNA, Messenger