ArticleScientific reports2022
eNAMPT neutralization reduces preclinical ARDS severity via rectified NFkB and Akt/mTORC2 signaling.
Article in Scientific reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 43 citations in OpenAlex.
- Development of a peripheral blood transcriptomic gene signature to predict bronchopulmonary dysplasia.American journal of physiology. Lung cellular and molecular physiology · 2023Trial
- Article
- Research progress on biomarkers of blast lung injury: Transition from traditional indicators to novel molecular markers.iScience · 2026Review
- Utility of Circulating Extracellular Nicotinamide Phosphoribosyltransferase and Its Association with Acute Respiratory Distress Syndrome Onset and Mortality: A Systematic Review and Meta-analysis.Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2026Article
- Activation of the impaired NAMPT/SIRT7/SOD2 axis restores alveolar progenitor cell renewal in idiopathic pulmonary fibrosis.The Journal of clinical investigation · 2026Article
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- Article
- Revisiting ventilator-induced lung injury: from mechanical power to immunometabolic interaction.Frontiers in immunology · 2026Review
- eNAMPT Is a Novel DAMP and Therapeutic Target in Human and Murine Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2025Article
- Predictive modeling of ARDS mortality integrating biomarker/cytokine, clinical and metabolomic data.Translational research : the journal of laboratory and clinical medicine · 2025Article
- Ventilator-induced lung injury in rat models: are they all equal in the race?Laboratory animal research · 2025Review
- NEDD4 E3 ligase-catalyzed NAMPT ubiquitination and autophagy activation are essential for pyroptosis-independent NAMPT secretion in human monocytes.Cell communication and signaling : CCS · 2025Article
- NAD World 3.0: the importance of the NMN transporter and eNAMPT in mammalian aging and longevity control.npj aging · 2025Review
- Chemokines as potential biomarkers for predicting the course of COVID-19 - a review of the literature.Frontiers in immunology · 2025Review
- Anti-DAMP therapies for acute inflammation.Frontiers in immunology · 2025Review
- Lung-Brain Axis-Generated Inflammatory Biomarkers in Traumatic Brain Injury and Acute Respiratory Distress Syndrome: Role of Mechanical Ventilation/Stress.Advances in biomarker sciences and technology · 2025Article
- Safety, Tolerability and Pharmacokinetics of the eNAMPT-Neutralizing ALT-100 Mab in Healthy Volunteers.Journal of clinical research and clinical trials · 2024Article
- Article
- Extracellular Nicotinamide Phosphoribosyltransferase Is a Therapeutic Target in Experimental Necrotizing Enterocolitis.Biomedicines · 2024Article
- Impact of Immunopathy and Coagulopathy on Multi-Organ Failure and Mortality in a Lethal Porcine Model of Controlled and Uncontrolled Hemorrhage.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
22 authors at 4 institutions in 1 country.
Funding
Abstract
Despite encouraging preclinical data, therapies to reduce ARDS mortality remains a globally unmet need, including during the COVID-19 pandemic. We previously identified extracellular nicotinamide phosphoribosyltransferase (eNAMPT) as a novel damage-associated molecular pattern protein (DAMP) via TLR4 ligation which regulates inflammatory cascade activation. eNAMPT is tightly linked to human ARDS by biomarker and genotyping studies in ARDS subjects. We now hypothesize that an eNAMPT-neutralizing mAb will significantly reduce the severity of ARDS lung inflammatory lung injury in diverse preclinical rat and porcine models. Sprague Dawley rats received eNAMPT mAb intravenously following exposure to intratracheal lipopolysaccharide (LPS) or to a traumatic blast (125 kPa) but prior to initiation of ventilator-induced lung injury (VILI) (4 h). Yucatan minipigs received intravenous eNAMPT mAb 2 h after initiation of septic shock and VILI (12 h). Each rat/porcine ARDS/VILI model was strongly associated with evidence of severe inflammatory lung injury with NFkB pathway activation and marked dysregulation of the Akt/mTORC2 signaling pathway. eNAMPT neutralization dramatically reduced inflammatory indices and the severity of lung injury in each rat/porcine ARDS/VILI model (~ 50% reduction) including reduction in serum lactate, and plasma levels of eNAMPT, IL-6, TNFα and Ang-2. The eNAMPT mAb further rectified NFkB pathway activation and preserved the Akt/mTORC2 signaling pathway. These results strongly support targeting the eNAMPT/TLR4 inflammatory pathway as a potential ARDS strategy to reduce inflammatory lung injury and ARDS mortality.
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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.