ArticleAmerican journal of physiology. Lung cellular and molecular physiology2017
Dysregulated Nox4 ubiquitination contributes to redox imbalance and age-related severity of acute lung injury.
Article in American journal of physiology. Lung cellular and molecular physiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- Lung-Protective Ventilation Strategies for Relief from Ventilator-Associated Lung Injury in Patients Undergoing Craniotomy: A Bicenter Randomized, Parallel, and Controlled Trial.Oxidative medicine and cellular longevity · 2017Trial
- Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced pulmonary endothelial barrier dysfunction by activating TXNDC5.Journal of advanced research · 2026Article
- NADPH oxidases in immunometabolism and disease pathology: mechanistic networks, pollutant triggers, and therapeutic frontiers.Cellular & molecular immunology · 2026Review
- Pulmonary edema following subarachnoid hemorrhage is associated with impairment of pulmonary vascular endothelial glycocalyx.Biochemistry and biophysics reports · 2026Article
- The Role of NADPH Oxidase 4 in Neutrophil-Mediated Immune Escape in Gastric Cancer.International journal of biological sciences · 2026Article
- Aging and lung diseases: Unraveling mechanisms and therapeutic targets.Chinese medical journal pulmonary and critical care medicine · 2025Review
- Redox Regulation of Microvascular Physiology and Pathophysiology: Insights into Therapeutic Strategies and Limitations.Antioxidants & redox signaling · 2025Review
- Inhibition of NOX4-Mediated ROS Production Contributes to Selenomethionine's Anti-Inflammatory Effect in LPS-Stimulated Bovine Endometrial Epithelial Cells.Veterinary sciences · 2025Article
- Low-molecular-weight heparin ameliorates intestinal barrier dysfunction in aged male rats via protection of tight junction proteins.Biogerontology · 2024Article
- A Razor's Edge: Vascular Responses to Acute Inflammatory Lung Injury/Acute Respiratory Distress Syndrome.Annual review of physiology · 2024Review
- Aloe-emodin plus TIENAM ameliorate cecal ligation and puncture-induced sepsis in mice by attenuating inflammation and modulating microbiota.Frontiers in microbiology · 2024Article
- ARDS and aging: TYMS emerges as a promising biomarker and therapeutic target.Frontiers in immunology · 2024Article
- The m6A reader YTHDF2 alleviates the inflammatory response by inhibiting IL-6R/JAK2/STAT1 pathway-mediated high-mobility group box-1 release.Burns & trauma · 2023Article
- Article
- TLR4 activation induces inflammatory vascular permeability via Dock1 targeting and NOX4 upregulation.Biochimica et biophysica acta. Molecular basis of disease · 2022Article
- NADPH oxidase 4 signaling in a ventilator-induced lung injury mouse model.Respiratory research · 2022Article
- Lung-Targeted Delivery of Dimethyl Fumarate Promotes the Reversal of Age-Dependent Established Lung Fibrosis.Antioxidants (Basel, Switzerland) · 2022Article
- Poldip2/Nox4 Mediates Lipopolysaccharide-Induced Oxidative Stress and Inflammation in Human Lung Epithelial Cells.Mediators of inflammation · 2022Article
- Mechanistic Understanding of Lung Inflammation: Recent Advances and Emerging Techniques.Journal of inflammation research · 2022Review
- Redox Dysregulation in Aging and COPD: Role of NOX Enzymes and Implications for Antioxidant Strategies.Antioxidants (Basel, Switzerland) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Acute respiratory distress syndrome (ARDS) is a devastating critical illness disproportionately affecting the elderly population, with both higher incidence and mortality. The integrity of the lung endothelial cell (EC) monolayer is critical for preservation of lung function. However, mechanisms mediating EC barrier regulation in the context of aging remain unclear. We assessed the severity of acute lung injury (ALI) in young (2 mo) and aged (18 mo) mice using a two-hit preclinical model. Compared with young cohorts, aged mice exhibited increased ALI severity, with greater vascular permeability characterized by elevated albumin influx and levels of bronchoalveolar lavage (BAL) cells (neutrophils) and protein. Aged/injured mice also demonstrated elevated levels of reactive oxygen species (ROS) in the BAL, which was associated with upregulation of the ROS-generating enzyme, Nox4. We evaluated the role of aging in human lung EC barrier regulation utilizing a cellular model of replicative senescence. Senescent EC populations were defined by increases in β-galactosidase activity and p16 levels. In response to lipopolysaccharide (LPS) challenge, senescent ECs demonstrate exacerbated permeability responses compared with control "young" ECs. LPS challenge led to a rapid induction of Nox4 expression in both control and senescent ECs, which was posttranslationally mediated via the proteasome/ubiquitin system. However, senescent ECs demonstrated deficient Nox4 ubiquitination, resulting in sustained expression of Nox4 and alterations in cellular redox homeostasis. Pharmacological inhibition of Nox4 in senescent ECs reduced LPS-induced alterations in permeability. These studies provide insight into the roles of Nox4/senescence in EC barrier responses and offer a mechanistic link to the increased incidence and mortality of ARDS associated with aging.
Indexed as
Identifiers
What OpenQuestion holds
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.