Abstract
COPD is characterized by emphysema with loss of extracellular matrix (ECM), and (small) airways disease with increased ECM deposition and airway wall thickening. How both processes can occur in close proximity in one lung is unknown and needs more attention. Fibroblasts are the principal cells involved in ECM production in the lung. MicroRNAs are small RNAs that can cause downregulation of target protein expression. We hypothesize that microRNA-mediated differences between COPD and healthy fibroblasts, and additionally airway and parenchymal fibroblasts, contribute to the airway and parenchymal changes in COPD.
We profiled microRNA expression in pulmonary fibroblasts from severe COPD patients and controls to investigate effects of COPD, smoking (ex-smokers vs current smokers) and fibroblast type (airway vs parenchymal fibroblasts).
Using linear models we found 42 microRNAs differentially expressed in COPD patients, 25 between ex-smokers and current smokers and 45 between airway and parenchymal fibroblasts in COPD (p<0.01). Interestingly some of the microRNAs differentially expressed in COPD fibroblasts, i.e. mir-181d and mir-296-5p, are also differentially expressed in lung tissue in relation to emphysema severity (Christenson, S.A. et al. Am J Resp Crit Care Med 2010;181:A2024). COPD and smoking had similar effects on several microRNAs, including mir-181d, mir-296-5p, mir-29b1*, mir-23* and mir-202, suggesting a possible mechanism for the link between smoking and COPD development. Furthermore, mir-155 expression was decreased in COPD and within COPD in airway fibroblasts. Given the role of mir-155 in airway remodeling (Rodriguez, A. et al. Science 2007; 316:608-11) this microRNA could be important in the airway changes in COPD.
- © 2011 ERS
