Table 2.
Involvement of NADPH Oxidase Enzymes in Profibrotic Processes In Vitro, In Vivo, and in Idiopathic Pulmonary Fibrosis Patients
| NADPH oxidase | Cell/tissue type | Model | DUOX/NOX activity | Key finding | Reference |
|---|---|---|---|---|---|
| NOX1 | Human pulmonary artery endothelial cells | Radiation | Increased | NOX1 inhibition by shRNA reduces intracellular ROS and reduced phenotypic changes | (38) |
| C57BL/6 mice | Radiation | Increased | NOX1 is associated with profibrotic gene expression | (38) | |
| NOX2 | BALF mice | BLM | Increased | NOX2-deficient mice show a moderate protection from bleomycin-induced lung fibrosis | (137) |
| C57BL/6 gp91phox−/− mice | Carbon nanotubes | Increased | NOX2 deficiency is associated with the suppression of the profibrotic response, with decreased TGF-β and lower levels of collagen deposition | (210) | |
| NOX4 | Human lung fibroblasts | TGF | Increased | NOX4 regulates myofibroblast differentiation | (77) |
| Human alveolar epithelial cells | BLM | Increased | NOX4 is a key player in epithelial cell death | (32) | |
| Mouse fibroblasts | BLM | Increased | NOX4 mediates senescence and apoptosis resistance | (76) | |
| Human pulmonary smooth muscle cells | IPF patients | Increased | NOX4 is expressed in thickened pulmonary arteries | (165) | |
| Mouse fibroblasts and human fibroblasts | BLM | Increased | NOX4 is increased in senescent fibroblasts and contributes to apoptosis resistance | (76) | |
| IPF patients | |||||
| Human lung fibroblasts | IPF patients | Increased | NOX4 mediates differentiation into myofibroblasts | (6) |
BLM, bleomycin; DUOX, dual oxidase; NOX, NADPH oxidase; ROS, reactive oxygen species; TGF-β, transforming growth factor β.