Increased human Ca2+-activated Cl- channel 1 expression and mucus overproduction in airway epithelia of smokers and chronic obstructive pulmonary disease patients
- Equal contributors
1 Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 2-26-1, Muraoka-higashi, Fujisawa, Kanagawa, 251-8555, Japan
2 Department of Clinical Laboratory Sciences, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano, 390-8621, Japan
3 The First Department of Internal Medicine, Shinshu University School of Medicine, 3-1-1, Asahi, Matsumoto, Nagano, 390-8621, Japan
Respiratory Research 2012, 13:55 doi:10.1186/1465-9921-13-55Published: 25 June 2012
The mechanisms underlying the association between smoking and mucus overproduction remain unknown. Because of its involvement in other airway diseases, such as asthma, we hypothesized that Ca2+-activated Cl- channel 1 (CLCA1) was associated with overproduction of mucus in the airways of smokers and COPD patients.
Using real-time quantitative PCR analyses, we compared the CLCA1 mRNA expression levels in induced-sputum cells from COPD patients (n = 20), smokers without COPD (n = 5), and non-smokers (n =13). We also examined the relationship between CLCA1 protein expression and mucus production in lung airway epithelia of COPD patients (n = 6), smokers without COPD (n = 7), and non-smokers (n = 7).
CLCA1 mRNA expression was significantly up-regulated in the induced-sputum cells of COPD patients compared with cells of non-smokers (p = 0.02), but there was no significant difference compared with cells of smokers without COPD. Using immunostaining with an anti-CLCA1 antibody, semi-quantitative image analyses of airway epithelium demonstrated significantly increased CLCA1 expression in smokers without COPD (p = 0.02) and in COPD patients (p = 0.002) compared with non-smokers. There were significant negative correlations between CLCA1 protein expression and FEV1/FVC (r = −0.57, p = 0.01) and %predicted FEV1 (r = −0.56, p = 0.01). PAS staining for mucus showed that there was a significant positive correlation between CLCA1 protein expression and mucus production (r = 0.67, p = 0.001). These markers were significantly increased in smokers without COPD (p = 0.04) and in COPD patients (p = 0.003) compared with non-smokers (non-smokers < smokers ≤ COPD).
CLCA1 expression is significantly related to mucus production in the airway epithelia of smokers and COPD patients, and may contribute to the development and pathogenesis of COPD by inducing mucus production.