Expression of Connective Tissue Growth Factor and Bone Morphogenetic Protein-7 in Pseudomonas aeruginosa-induced Chronic Obstructive Pulmonary Disease in Rats

Abstract

Repeated intratracheal injection of Pseudomonas aeruginosa (PA) in male Wistar rats was used to investigate the role of chronic infection in the development of chronic obstructive pulmonary disease (COPD) and the possible involvement of connective tissue growth factor (CTGF) and bone morphogenetic protein-7 (BMP-7) in this process. Injections of PA or normal saline solution were given for 8 weeks and the rats observed for a further 8 weeks. In addition to arterial blood gas, lung function and lung pathology measurement during this time period, protein and mRNA expression of CTGF and BMP-7 were measured, and the correlation of expression of CTGF and BMP-7 with pathological changes in the lung was evaluated. Repeated intratracheal PA infection in rats caused reduction in body weight, hypoxia, carbon dioxide retention, compromised lung function, chronic inflammation, thickening of the tracheal and arterial walls, and emphysema, changes consistent with those of COPD. Rats with PA infection also had increased CTGF and decreased BMP-7 expression, suggesting that both CTGF and BMP-7 are involved in the occurrence and development of airway remodeling. Our findings suggest that repeated airway infection is not only a factor resulting in deterioration of COPD, but is also a risk factor for its development, and that CTGF and BMP-7 are involved in the pathogenesis of this condition.