ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
An endothelial TLR4-VEGFR2 pathway mediates lung protection against oxidant-induced injury.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 15 citations in OpenAlex.
- MicroRNA-1 protects the endothelium in acute lung injury.JCI insight · 2023Article
- Oxygen toxicity: cellular mechanisms in normobaric hyperoxia.Cell biology and toxicology · 2023Review
- miR-181c-5p mediates apoptosis of vascular endothelial cells induced by hyperoxemia via ceRNA crosstalk.Scientific reports · 2021Article
- 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
- SU5416 attenuated lipopolysaccharide-induced acute lung injury in mice by modulating properties of vascular endothelial cells.Drug design, development and therapy · 2019Article
- Mice Lacking the Cytochrome P450 1B1 Gene Are Less Susceptible to Hyperoxic Lung Injury Than Wild Type.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- VEGF mitigates histone-induced pyroptosis in the remote liver injury associated with renal allograft ischemia-reperfusion injury in rats.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2018Article
- Oxidative stress diseases unique to the perinatal period: A window into the developing innate immune response.American journal of reproductive immunology (New York, N.Y. : 1989) · 2018Review
- Lung Endothelial MicroRNA-1 Regulates Tumor Growth and Angiogenesis.American journal of respiratory and critical care medicine · 2017Article
- Article
- Mesenchymal Stem Cells Promoted Lung Wound Repair through Hox A9 during Endotoxemia-Induced Acute Lung Injury.Stem cells international · 2017Article
- An Endothelial Hsp70-TLR4 Axis Limits Nox3 Expression and Protects Against Oxidant Injury in Lungs.Antioxidants & redox signaling · 2016Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
TLR4 deficiency causes hypersusceptibility to oxidant-induced injury. We investigated the role of TLR4 in lung protection, using used bone marrow chimeras; cell-specific transgenic modeling; and lentiviral delivery in vivo to knock down or express TLR4 in various lung compartments; and lung-specific VEGF transgenic mice to investigate the effect of TLR4 on VEGF-mediated protection. C57/BL6 mice were exposed to 100% oxygen in an enclosed chamber and assessed for survival and lung injury. Primary endothelial cells were stimulated with recombinant VEGF and exposed to hyperoxia or hydrogen peroxide. Endothelium-specific expression of human TLR4 (as opposed to its expression in epithelium or immune cells) increased the survival of TLR4-deficent mice in hyperoxia by 24 h and decreased LDH release and lung cell apoptosis after 72 h of exposure by 30%. TLR4 expression was necessary and sufficient for the protective effect of VEGF in the lungs and in primary endothelial cells in culture. TLR4 knockdown inhibited VEGF signaling through VEGF receptor 2 (VEGFR2), Akt, and ERK pathways in lungs and primary endothelial cells and decreased the availability of VEGFR2 at the cell surface. These findings demonstrate a novel mechanism through which TLR4, an innate pattern receptor, interacts with an endothelial survival pathway.
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Registered trials
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