The effects of NOX4 and TGF-βinvolved in airway remodeling of Chronic Obstructive Pulmonary Disease

Abstract

To investigate the role of nicotinamide adenine dinucleotide phosphate 4 (NADPH4,NOX4) and transforming growth factor-beta (TGF-β) involve in pathogenesis of airway remodeling in chronic obstructive pulmonary disease (COPD). Lung tissues from 36 COPD patients and 19 patients with normal lung function were enrolled in this study. The volume of airway smooth muscle (ASM)mass was evaluated. The expressions of NOX4, collagen Ⅳ (Col Ⅳ) and TGF-β were tested by a semi-quantitative morphological and/or immunohistochemistry staining method and Western blot, and their correlations with pulmonary functions were analyzed. ①Index of the percentage of the thickness of ASM/external diameter of small airway (WT%) and the percentage of the area of ASM/transverse area of small airway (WA%) were significantly higher in the COPD group than those in controls(P<0.05).②In COPD patients,epithelial cells metaplasia were found and α-SMA and Col Ⅳwere expressed in a part of epithelial cells. The expressions of α-small muscle actin (α-SMA) and Col Ⅰ were increased in COPD patients in comparison with the patients without obstructive airway disorders(P<0.05).③The expression of NOX4 in ASM and epithelial cells of COPD patients was significantly higher in comparison with the patients without COPD. The expression of NOX4 in ASM of small airway were statistically different among different COPD grade (P<0.05). Correlation analysis demonstrated that the level of NOX4 protein in ASM of small airway was inversely associated with pulmonary functions. ④The expression of TGF-β in COPD was significantly higher than that in patients without COPD. ⑤ Correlation analysis demonstrated that the level of NOX4 protein in ASM of small airway, WT% and WA% were inversely associated with pulmonary functions. ①The airway remodeling of COPD is characterized by increasing hyperplasia of small airway smooth muscle.②Remodeling of airway smooth muscle associats with severity of airflow limitation in COPD patients. ③The expressions of NOX4, TGF-β and α-SMA in COPD epithelial cells and small airway smooth muscle cells are significantly enhanced. The expressions of NOX4, α-SMA and TGF-β are positively correlated with the severity of chronic obstructive pulmonary air flow, suggesting that TGF-β and NOX4 signaling may be involved in the development of chronic obstructive pulmonary disease airway remodeling.