ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Hyperoxia-induced p47phox activation and ROS generation is mediated through S1P transporter Spns2, and S1P/S1P1&2 signaling axis in lung endothelium.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 36 citations in OpenAlex.
- Mechanistic insights and therapeutic potential of sphingosine‑1‑phosphate in the development of pulmonary fibrosis (Review).Molecular medicine reports · 2026Review
- Unfolded protein response in bronchopulmonary dysplasia: mechanisms, pathways, and therapeutic implications.Frontiers in cell and developmental biology · 2026Review
- Bronchopulmonary dysplasia demonstrates dysregulated autotaxin/lysophosphatidic acid signaling in a neonatal mouse model.Pediatric research · 2025Article
- Decoding STAT3: a new frontier in understanding and treating hyperoxic lung injury.Frontiers in immunology · 2025Review
- Sphingosine kinase 1-specific inhibitor PF543 reduces goblet cell metaplasia of bronchial epithelium in an acute asthma model.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Cross-Regulation of the Cellular Redox System, Oxygen, and Sphingolipid Signalling.Metabolites · 2023Review
- Sphingolipids in mitochondria-from function to disease.Frontiers in cell and developmental biology · 2023Review
- Targeting SPHK1/PBX1 Axis Induced Cell Cycle Arrest in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2022Article
- [Research advances of the roles of sphingosine-1-phosphate in acute lung injury].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Review
- Sphingosine 1-phosphate and its regulatory role in vascular endothelial cells.Histology and histopathology · 2022Review
- NOX4 Mediates Epithelial Cell Death in Hyperoxic Acute Lung Injury Through Mitochondrial Reactive Oxygen Species.Frontiers in pharmacology · 2022Article
- Sphingosine kinase 1 regulates lysyl oxidase through STAT3 in hyperoxia-mediated neonatal lung injury.Thorax · 2022Article
- Metabolic dysregulation in bronchopulmonary dysplasia: Implications for identification of biomarkers and therapeutic approaches.Redox biology · 2021Article
- S1P/S1PAntioxidants (Basel, Switzerland) · 2021Article
- Article
- Hyperoxia-induced S1PCell biochemistry and biophysics · 2021Article
- miR-181c-5p mediates apoptosis of vascular endothelial cells induced by hyperoxemia via ceRNA crosstalk.Scientific reports · 2021Article
- Hyperoxia and Lungs: What We Have Learned From Animal Models.Frontiers in medicine · 2021Review
- Neonatal therapy with PF543, a sphingosine kinase 1 inhibitor, ameliorates hyperoxia-induced airway remodeling in a murine model of bronchopulmonary dysplasia.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Advancements in understanding the role of lysophospholipids and their receptors in lung disorders including bronchopulmonary dysplasia.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2020Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperoxia-induced lung injury adversely affects ICU patients and neonates on ventilator assisted breathing. The underlying culprit appears to be reactive oxygen species (ROS)-induced lung damage. The major contributor of hyperoxia-induced ROS is activation of the multiprotein enzyme complex NADPH oxidase. Sphingosine-1-phosphate (S1P) signaling is known to be involved in hyperoxia-mediated ROS generation; however, the mechanism(s) of S1P-induced NADPH oxidase activation is unclear. Here, we investigated various steps in the S1P signaling pathway mediating ROS production in response to hyperoxia in lung endothelium. Of the two closely related sphingosine kinases (SphKs)1 and 2, which synthesize S1P from sphingosine, only Sphk1(-/-) mice conferred protection against hyperoxia-induced lung injury. S1P is metabolized predominantly by S1P lyase and partial deletion of Sgpl1 (Sgpl1(+/-)) in mice accentuated lung injury. Hyperoxia stimulated S1P accumulation in human lung microvascular endothelial cells (HLMVECs), and downregulation of S1P transporter spinster homolog 2 (Spns2) or S1P receptors S1P1&2, but not S1P3, using specific siRNA attenuated hyperoxia-induced p47(phox) translocation to cell periphery and ROS generation in HLMVECs. These results suggest a role for Spns2 and S1P1&2 in hyperoxia-mediated ROS generation. In addition, p47(phox) (phox:phagocyte oxidase) activation and ROS generation was also reduced by PF543, a specific SphK1 inhibitor in HLMVECs. Our data indicate a novel role for Spns2 and S1P1&2 in the activation of p47(phox) and production of ROS involved in hyperoxia-mediated lung injury in neonatal and adult mice.
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