ArticleProceedings of the National Academy of Sciences of the United States of America2005
Activation of hypoxia-inducible factors in hyperoxia through prolyl 4-hydroxylase blockade in cells and explants of primate lung.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 89 citations in OpenAlex.
- Interplay of hypoxia-inducible factors and oxygen therapy in cardiovascular medicine.Nature reviews. Cardiology · 2023Review
- Hypoxia-Inducible Factor-1α in SM22α-Expressing Cells Modulates Alveolarization.American journal of respiratory cell and molecular biology · 2023Article
- Oxygen toxicity: cellular mechanisms in normobaric hyperoxia.Cell biology and toxicology · 2023Review
- Hyperoxia Induced Hypomyelination.Biomedicines · 2022Article
- SM22α cell-specific HIF stabilization mitigates hyperoxia-induced neonatal lung injury.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Danlou Tablet Improves Chronic Intermittent Hypoxia-Induced Dyslipidemia and Arteriosclerosis by HIF-1α-Angptl4 mRNA Signaling Pathway.Chinese journal of integrative medicine · 2022Article
- Hypoxia-Induced Alpha-Globin Expression in Syncytiotrophoblasts Mimics the Pattern Observed in Preeclamptic Placentas.International journal of molecular sciences · 2021Article
- Cellular clocks in hyperoxia effects on [CaAmerican journal of physiology. Lung cellular and molecular physiology · 2021Article
- Hyperoxia-induced bronchopulmonary dysplasia: better models for better therapies.Disease models & mechanisms · 2021Review
- Thiol-Redox Regulation in Lung Development and Vascular Remodeling.Antioxidants & redox signaling · 2019Review
- Caffeine is associated with improved alveolarization and angiogenesis in male mice following hyperoxia induced lung injury.BMC pulmonary medicine · 2019Article
- Repressive role of stabilized hypoxia inducible factor 1α expression on transforming growth factor β-induced extracellular matrix production in lung cancer cells.Cancer science · 2019Article
- Angiopoietin-like protein 2 is an important facilitator of tumor proliferation, metastasis, angiogenesis and glycolysis in osteosarcoma.American journal of translational research · 2019Article
- Effect of Hypoxia on the Pathogenesis of Acinetobacter baumannii and Pseudomonas aeruginosa In Vitro and in Murine Experimental Models of Infection.Infection and immunity · 2018Article
- 3-Hydroxypyruvate Destabilizes Hypoxia Inducible Factor and Induces Angiostasis.Investigative ophthalmology & visual science · 2018Article
- Aerosolized deferoxamine administration in mouse model of bronchopulmonary dysplasia improve pulmonary development.American journal of translational research · 2018Article
- Hyperoxia provokes a time- and dose-dependent inflammatory response in mechanically ventilated mice, irrespective of tidal volumes.Intensive care medicine experimental · 2017Article
- Sexual dimorphism of the pulmonary transcriptome in neonatal hyperoxic lung injury: identification of angiogenesis as a key pathway.American journal of physiology. Lung cellular and molecular physiology · 2017Article
- Sex-specific differences in the modulation of Growth Differentiation Factor 15 (GDF15) by hyperoxia in vivo and in vitro: Role of Hif-1α.Toxicology and applied pharmacology · 2017Article
- Forkhead Transcription Factor 3a (FOXO3a) Modulates Hypoxia Signaling via Up-regulation of the von Hippel-Lindau Gene (VHL).The Journal of biological chemistry · 2016Article
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
Preterm neonates with respiratory distress syndrome (RDS) often develop a chronic form of lung disease called bronchopulmonary dysplasia (BPD), characterized by decreased alveolar and vascular development. Ventilator treatment with supraphysiological O2 concentrations (hyperoxia) contribute to the development of BPD. Hyperoxia down-regulates and hypoxia up-regulates many angiogenic factors in the developing lung. We investigated whether angiogenic responses could be augmented through enhancement of hypoxia-inducible factors 1alpha and 2alpha (HIF-1alpha and -2alpha, respectively) via blockade of prolyl hydroxylase domain-containing proteins (HIF-PHDs) in human microvascular endothelial cells from developing and adult lung, in epithelial A549 cells, and in fetal baboon explants in relative or absolute hyperoxia. PHD inhibitor (FG-4095) and positive control dimethyloxaloylglycine (DMOG), selective and nonselective HIF-PHD inhibitors, respectively, enhanced HIF-1alpha and -2alpha, vascular endothelial growth factor (VEGF), and platelet-endothelial cell adhesion molecule 1 expression in vitro in 95% and 21% O2. Furthermore, VEGF receptor fms-like tyrosine kinase 1 (Flt-1) was elevated, whereas kinase insert domain-containing receptor/fetal liver kinase 1 (KDR) was diminished in endothelial, but not epithelial, cells. Intracellular Flt-1 and KDR locations were unchanged by PHD blockade. Like VEGF, FG-4095 and DMOG increased angiogenesis in vitro, both in 95% and 21% O2, an effect that could be blocked through either Flt-1 or KDR. Notably, FG-4095 was effective in stimulating HIFs and VEGF also in fetal baboon lung explants. FG-4095 or DMOG treatment appeared to stimulate the feedback loop promoting HIF degradation in that PHD-2 and/or -3, but not PHD-1, were enhanced. Through actions characterized above, FG-4095 could have desirable effects in enhancing lung growth in BPD.
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