ArticleAntioxidants & redox signaling2016
An Endothelial Hsp70-TLR4 Axis Limits Nox3 Expression and Protects Against Oxidant Injury in Lungs.
Article in Antioxidants & redox signaling, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 22 citations in OpenAlex.
- Advances in research on hyperoxia-induced acute lung injury: from pathogenesis to therapy.Frontiers in cell and developmental biology · 2026Review
- Nox3 expression and function in retinal ganglion cells and Amacrine cells.Cellular and molecular life sciences : CMLS · 2025Article
- Targeted Regulation of HSP70 by the ARP2/3 Complex in Mammary Epithelial Cells and Its Impact on Host Cell Apoptosis.Biomolecules · 2025Article
- NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024Review
- Extracellular Heat Shock Protein 70 Increases the Glucocorticoid Receptor and Dual-Specificity Phosphatase 1 via Toll-like Receptor 4 and Attenuates Inflammation in Airway Epithelial Cells.International journal of molecular sciences · 2023Article
- NADPH oxidase family proteins: signaling dynamics to disease management.Cellular & molecular immunology · 2022Review
- HSP70 as a biomarker of the thin threshold between benefit and injury due to physical exercise when exposed to air pollution.Cell stress & chaperones · 2021Review
- Oxidative Stress and Hypertension.Circulation research · 2021Review
- Expression of heat shock protein 70 and Annexin A1 in serum of patients with acutely severe traumatic brain injury.Experimental and therapeutic medicine · 2020Article
- Novel Regulators and Targets of Redox Signaling in Pulmonary Vasculature.Current opinion in physiology · 2019Article
- Endothelial toll-like receptor 4 maintains lung integrity via epigenetic suppression of p16Aging cell · 2019Article
- Endothelial Stanniocalcin 1 Maintains Mitochondrial Bioenergetics and Prevents Oxidant-Induced Lung Injury via Toll-Like Receptor 4.Antioxidants & redox signaling · 2019Article
- Regulation of Smooth Muscle Cell Proliferation by NADPH Oxidases in Pulmonary Hypertension.Antioxidants (Basel, Switzerland) · 2019Review
- Genome-wide association study identifies loci and candidate genes for non-idiopathic pulmonary hypertension in Eastern Chinese Han population.BMC pulmonary medicine · 2018Article
- Gestational Hypoxia and Developmental Plasticity.Physiological reviews · 2018Review
- Progranulin Recruits HSP70 to β-Glucocerebrosidase and Is Therapeutic Against Gaucher Disease.EBioMedicine · 2016Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsOxidants play a critical role in the pathogenesis of acute lung injury (ALI). Nox3 is a novel member of the NADPH oxidase (Nox) family of oxidant-generating enzymes, which our laboratory had previously identified to be induced in the lungs of TLR4(-/-) mice. However, the physiologic role of Nox3 induction in lungs and its precise relationship to TLR4 are unknown. Furthermore, the cell compartment involved and the signaling mechanisms of Nox3 induction are unknown.
resultsWe identified that Nox3 is regulated by heat shock protein 70 (Hsp70) signaling via a TLR4-Trif-signal transducer and activator of transcription 3 (Stat3) pathway and that Nox3 induction leads to increased oxidant injury and death in mice and lung endothelial cells. We generated Nox3(-/-)/TLR4(-/-) double knockout mice, endothelial-targeting lentiviral silencing constructs, and endothelial-targeted Stat3(-/-) mice to specifically demonstrate that Nox3 induction is responsible for the pro-oxidant, proapoptotic phenotype of TLR4(-/-) mice. We also show that an endothelial Hsp70-TLR4-Trif-Stat3 axis is required to suppress deleterious Nox3 induction. INNOVATION: To date, a physiologic role for Nox3 in oxidant-induced ALI has not been identified. In addition, we generated unique double knockout mice and endothelial-targeted lentiviral silencing constructs to specifically demonstrate the role of a TLR4 signaling pathway in regulating pro-oxidant generation.
conclusionsWe identified an endothelial TLR4-Trif antioxidant pathway that leads to the inhibition of a novel NADPH oxidase, Nox3, in lungs and lung endothelial cells. We also identified the role of a TLR4 ligand, Hsp70, in suppressing Nox3 in basal and pro-oxidant conditions. These studies identify potentially new therapeutic targets in oxidant-induced ALI. Antioxid. Redox Signal. 24, 991-1012.
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