ArticleRespiratory research2016
Airway smooth muscle NOX4 is upregulated and modulates ROS generation in COPD.
Article in Respiratory research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 48 citations in OpenAlex.
- Association of glutathione S-transferase M1 and T1 genotypes with asthma: A meta-analysis.Medicine · 2020Pooled it
- ROS scavenging mitigates TNFα-induced endoplasmic reticulum stress and mitochondrial fragmentation in human airway smooth muscle.Function (Oxford, England) · 2026Article
- Nox4 and circulating free MPO synergistically promote aortic aneurysm formation.Scientific reports · 2026Article
- Ironing out COPD: ferroptosis-driven immune dysregulation, metabolic rewiring, and precision therapeutic opportunities.Frontiers in immunology · 2026Review
- Nicotinamide adenine dinucleotide phosphate oxidase 4 in lung disease: a review of its biology and therapeutic potential.Experimental biology and medicine (Maywood, N.J.) · 2026Review
- The Role of Oxidative Stress in the Pathogenesis of Childhood Asthma: A Comprehensive Review.Children (Basel, Switzerland) · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Cigarette Smoking-Induced Glucose Metabolic Reprogramming in Chronic Obstructive Pulmonary Disease: Mechanisms and Therapeutic Implications.International journal of chronic obstructive pulmonary disease · 2025Review
- Protective factors against oxidative stress in COPD: focus on Nrf2-dependent antioxidant gene expression.Frontiers in medicine · 2025Review
- ROS-mediated regulation of β2AR function: Does oxidation play a meaningful role towards β2-agonist tachyphylaxis in airway obstructive diseases?Biochemical pharmacology · 2024Review
- Rare coding variants in NOX4 link high ROS levels to psoriatic arthritis mutilans.EMBO molecular medicine · 2024Article
- Agonists and hydrogen peroxide mediate hyperoxidation of β2-adrenergic receptor in airway epithelial cells: Implications for tachyphylaxis to β2-agonists in constrictive airway disorders.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2023Article
- Reduction of TRPC1/TRPC3 mediated CaCellular signalling · 2023Article
- Cigarette Smoke-Induced Respiratory Response: Insights into Cellular Processes and Biomarkers.Antioxidants (Basel, Switzerland) · 2023Review
- The Role of Oxidative Stress and Antioxidants in Cardiovascular Comorbidities in COPD.Antioxidants (Basel, Switzerland) · 2023Review
- Airway Smooth Muscle Regulated by Oxidative Stress in COPD.Antioxidants (Basel, Switzerland) · 2023Review
- NADPH oxidase family proteins: signaling dynamics to disease management.Cellular & molecular immunology · 2022Review
- Chronic obstructive pulmonary disease and atherosclerosis: common mechanisms and novel therapeutics.Clinical science (London, England : 1979) · 2022Review
- Association ofCanadian respiratory journal · 2022Article
- Redox Dysregulation in Aging and COPD: Role of NOX Enzymes and Implications for Antioxidant Strategies.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The burden of oxidative stress is increased in chronic obstructive pulmonary disease (COPD). However, whether the intra-cellular mechanisms controlling the oxidant/anti-oxidant balance in structural airway cells such as airway smooth muscle in COPD is altered is unclear. We sought to determine whether the expression of the NADPH oxidase (NOX)-4 is increased in airway smooth muscle in COPD both in vivo and primary cells in vitro and its role in hydrogen peroxide-induced reactive oxygen species generation. We found that in vivo NOX4 expression was up-regulated in the airway smooth muscle bundle in COPD (n = 9) and healthy controls with >20 pack year history (n = 4) compared to control subjects without a significant smoking history (n = 6). In vitro NOX4 expression was increased in airway smooth muscle cells from subjects with COPD (n = 5) compared to asthma (n = 7) and upregulated following TNF-α stimulation. Hydrogen peroxide-induced reactive oxygen species generation by airway smooth muscle cells in COPD (n = 5) was comparable to healthy controls (n = 9) but lower than asthma (n = 5); and was markedly attenuated by NOX4 inhibition. Our findings demonstrate that NOX4 expression is increased in vivo and in vitro in COPD and although we did not observe an intrinsic increase in oxidant-induced reactive oxygen species generation in COPD, it was reduced markedly by NOX4 inhibition supporting a potential therapeutic role for NOX4 in COPD.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.