Fig. 3

The scheme illustrates the effect of COPD on tissue remodeling. A Activation of alveolar macrophage leads to upregulation in TGF-β1 expression, upregulated TGF-β1 triggers differentiation of fibroblast to myofibroblasts and endothelial and epithelial cells to mesenchymal cells (EMT) which leads to fibrosis. Moreover, overexpressed TGF-β1 leads to an increase in ROS production by NOX4 activation. B Under inflammatory conditions, bone marrow-derived monocytes can migrate to lung tissue and differentiate to alveolar macrophages and this is, in turn, activates neutrophils in the existence of LTB-4 and IL-8. Activated neutrophils degrade elastin and as a result occurrence of emphysema through impairing protease/anti-protease balance and upregulation of MMP 2, 9, and 12; on the other hand, upregulated MMP 2, 9, and 12 induced goblet cells hyperplasia. C T cells derived from endothelial cells in COPD-derived inflammation-induced expression of IL-4, IFN-γ, IL-13, and perforin which leads to triggering goblet cells hyperplasia via disrupting mucociliary clearance. D In COPD diseases cause to increase in oxidative stress in mitochondrial which finally leads to activation of apoptosis by inhibiting P53. NOX4: NADPH oxidase 4, ROS: reactive oxygen species, ECM: extracellular matrix, LTB-4: leukotriene B4, IL: interleukin, MMPs: matrix metalloproteinase, IFN- γ: interferon-gamma