Increased expression of human calcium-activated chloride channel 1 is correlated with mucus overproduction in the airways of Chinese patients with chronic obstructive pulmonary disease

Abstract

Chronic obstructive pulmonary disease (COPD) is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 (CaCC(1)) was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of CaCC(1) and mucus overproduction in the airway of Chinese patients with COPD, the expressions of CaCC(1), MUC5AC and mucus in bronchial tissues were examined. Bronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to July in 2004. Twenty-five patients were diagnosed as the patients with COPD overproduction, and other 20 were the control subjects. The expressions of CaCC(1), MUC5AC and mucin in bronchial tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization with digoxigenin (DIG)-labeled RNA probe, immunohistochemical and alcian blue-periodic acid Schiff (AB-PAS) staining, respectively. Compared with the control group, the stronger expressions of CaCC(1) were further detected throughout the bronchial tissues from patients with COPD (P < 0.01). Furthermore, the stronger expressions of the CaCC(1) mRNA were related to the severity of airflow obstruction. Samples from COPD showed a stronger staining for MUC5AC than those in control subjects (P < 0.01) and AB-PAS staining revealed more mucins in COPD patients' submucosal gland comparing with that in control subjects (P < 0.01). Expression levels of the CaCC(1) mRNA were respectively negatively correlated with the patients' forced expiratory volume in one second (FEV(1))/forced vital capacity (FVC) data, FEV(1)% predicted data, V(50)% predicted data, V(25)% predicted data (r = -0.43, r = -0.43, r = -0.35, r = -0.36, P < 0.01, P < 0.01, P < 0.05, P < 0.05). While the expression levels of the CaCC(1) mRNA were well correlated with the expression levels of the MUC5AC mRNA of airway epithelium and the PAS-AB stained area of submucosal glands (r = 0.39, r = 0.46, P < 0.05, P < 0.01). Expression levels of the MUC5AC mRNA were negatively correlated with the patients' FEV(1)/FVC data (P = 0.01), FEV(1)% pred data (P = 0.01), V(50)% predicted data, V(25)% predicted data (r = -0.53, r = -0.53, r = -0.48, r = -0.43, P < 0.01, P < 0.01, P < 0.01, P < 0.01). While the expression levels of the MUC5AC mRNA were well correlated with the positively PAS-AB stained area of submucosal gland (P < 0.05), and the correlation coefficients were 0.43. These results suggest that the stronger gene expression of CaCC(1) exists, complicated with mucus overproduction in the airway of Chinese patients with COPD.