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The Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidases in Lung Architecture Remodeling


The Role of Nicotinamide Adenine Dinucleotide Phosphate Oxidases in Lung Architecture Remodeling

Anantha Harijith et al. Antioxidants (Basel).


Chronic lung disorders, such as pulmonary artery hypertension (PAH), chronic obstructive pulmonary disease (COPD), asthma and neonatal bronchopulmonary dysplasia (BPD), are characterized by airway and/or vascular remodeling. Despite differences in the pathology, reactive oxygen species (ROS) have been highlighted as a critical contributor to the initiation and development of airway and vascular remodeling. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) appear to play a pivotal role in lung signaling, leading to marked changes in pulmonary airway and vascular cell phenotypes, including proliferation, hypertrophy and apoptosis. In this review, we summarized the current literature regarding the role of Nox in the airway and vascular remodeling.

Keywords: BPD; COPD; NADPH oxidase; PAH; asthma; remodeling.

Conflict of interest statement

The authors declare no conflict of interest.


Figure 1
Figure 1
Role of Nox in pulmonary artery hypertension (PAH). Nox1 and Nox4 expressed in human pulmonary artery endothelial cells (HPAECs) and pulmonary artery smooth muscle cells (PASMCs) are activated by various stimuli, among which hyperoxia and hypoxia are the most important ones. reactive oxygen species (ROS) generated by Nicotinamide adenine dinucleotide phosphate oxidases 1 (Nox1) and Nox4 stimulate cell proliferation, which is the major mechanism for PAH.
Figure 2
Figure 2
Role of Nox in asthma. Nox2, Nox4 and dual oxidase 1 (Duox1) play critical roles in asthma through various mechanisms. Both Duox1 and Nox4 stimulate mucus secretion and matrix metalloprotease (MMP) production in airway epithelial cells. In addition, Nuox1 enhances airway acidification and Nox4 induces ciliary dysfunction and airway smooth muscle hypercontractility. Nox2 plays distinctive roles in asthma. Nox2 expressed in myeloid and non-hematoietic cells plays distinctive roles in asthma. Nox2 expressed in myeloid cells is believed to mediate the worsened phenotype of asthma, while Nox2 expressed in the lung structure cells mediates airway eosinophilia.

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