ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Mitochondrial DNA damage-associated molecular patterns mediate a feed-forward cycle of bacteria-induced vascular injury in perfused rat lungs.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04445285 (Double Blind Randomized Phase 2 Placebo Controlled Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure), which is not on this map. Cited by 55 papers.
What it found
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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.
Double Blind Randomized Phase 2 Placebo Controlled Trial Using rhDNase to Reduce Mortality in COVID-19 Patients With Respiratory Failure
Who cites it
55 citing papers in PubMed, 77 citations in OpenAlex.
- Trial
- Oxidized mitochondrial DNA as a potential biomarker and mechanistic driver of autophagy-mitophagy dysregulation in pulmonary arterial hypertension: a narrative review.Molecular biology reports · 2026Review
- An improved analytic workflow for serum mtDNA DAMP abundance, fragmentation and heteroplasmic variants: a retrospective analysis of acute respiratory failure patients.Scientific reports · 2026Article
- Host mitochondrial DNA in bacterial pathogenesis: Friend, Foe, or Both?Archives of microbiology · 2026Review
- Cell-free mitochondrial DNA (cf-mtDNA) in human body fluids: molecular characteristics, release mechanisms, and clinical translation-an updated review.Frontiers in molecular biosciences · 2026Review
- Serum mtDNA DAMP abundance, fragmentation and heteroplasmic variants associate with Acute Respiratory Failure outcome: A secondary analysis of study NCT00976833.medRxiv : the preprint server for health sciences · 2025Article
- Mechanisms of lung crosstalk with end organs: scientific session V-ReSPIRE 2025.American journal of physiology. Lung cellular and molecular physiology · 2025Review
- Oxidative damage to lung mitochondrial DNA is a key contributor to the development of chemical lung injury.Redox biology · 2025Article
- Multidimensional study on mitochondrial dysfunction in pulmonary hypertension.Frontiers in medicine · 2025Review
- When DNA-damage responses meet innate and adaptive immunity.Cellular and molecular life sciences : CMLS · 2024Review
- Loss-of-function mitochondrial DNA polymerase gamma variants cause vascular smooth muscle cells to secrete a diffusible mitogenic factor.Frontiers in physiology · 2024Article
- Restoring the infected powerhouse: Mitochondrial quality control in sepsis.Redox biology · 2023Review
- Mitochondrial Dysfunction in Bacterial Infections.Pathogens (Basel, Switzerland) · 2023Review
- Mitochondrial DNA Release in Innate Immune Signaling.Annual review of biochemistry · 2023Review
- Mitochondria as a therapeutic: a potential new frontier in driving the shift from tissue repair to regeneration.Regenerative biomaterials · 2023Review
- Racial Differences in XO (Xanthine Oxidase) and Mitochondrial DNA Damage-Associated Molecular Patterns in Resistant Hypertension.Hypertension (Dallas, Tex. : 1979) · 2022Article
- Does acute and persistent metabolic dysregulation in COVID-19 point to novel biomarkers and future therapeutic strategies?The European respiratory journal · 2022Article
- Chronic Inhibition of Toll-Like Receptor 9 Ameliorates Pulmonary Hypertension in Rats.Journal of the American Heart Association · 2021Article
- Opioids Regulate the Immune System: Focusing on Macrophages and Their Organelles.Frontiers in pharmacology · 2021Review
- Through DNA sensors and hidden mitochondrial effects of SARS-CoV-2.The journal of venomous animals and toxins including tropical diseases · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Fragments of the mitochondrial genome released into the systemic circulation after mechanical trauma, termed mitochondrial DNA damage-associated molecular patterns (mtDNA DAMPs), are thought to mediate the systemic inflammatory response syndrome. The close association between circulating mtDNA DAMP levels and outcome in sepsis suggests that bacteria also might be a stimulus for mtDNA DAMP release. To test this hypothesis, we measured mtDNA DAMP abundance in medium perfusing isolated rat lungs challenged with an intratracheal instillation of 5 × 10(7) colony-forming units of Pseudomonas aeruginosa (strain 103; PA103). Intratracheal PA103 caused rapid accumulation of selected 200-bp sequences of the mitochondrial genome in rat lung perfusate accompanied by marked increases in both lung tissue oxidative mtDNA damage and in the vascular filtration coefficient (Kf). Increases in lung tissue mtDNA damage, perfusate mtDNA DAMP abundance, and Kf were blocked by addition to the perfusion medium of a fusion protein targeting the DNA repair enzyme Ogg1 to mitochondria. Intra-arterial injection of mtDNA DAMPs prepared from rat liver mimicked the effect of PA103 on both Kf and lung mtDNA integrity. Effects of mtDNA and PA103 on Kf were also attenuated by an oligodeoxynucleotide inhibitor of Toll-like receptor 9 (TLR-9) by mitochondria-targeted Ogg1 and by addition of DNase1 to the perfusion medium. Collectively, these findings are consistent with a model wherein PA103 causes oxidative mtDNA damage leading to a feed-forward cycle of mtDNA DAMP formation and TLR-9-dependent mtDNA damage that culminates in acute lung injury.
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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.