ArticleThe Journal of pharmacology and experimental therapeutics2015
Pharmacologic targeting of sphingosine-1-phosphate receptor 1 improves the renal microcirculation during sepsis in the mouse.
Article in The Journal of pharmacology and experimental therapeutics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 47 citations in OpenAlex.
- Immune molecular mechanisms of PANoptosis in sepsis-induced acute kidney injury.Inflammation and regeneration · 2026Review
- Pathophysiology and Management of Sepsis-associated Acute Kidney Injury.Clinics in chest medicine · 2026Review
- Automated production of radiotracer [Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine · 2025Article
- The role of phospholipid transfer protein in sepsis-associated acute kidney injury.Critical care (London, England) · 2025Observational
- Review
- Serotonin Signaling and the Hyperpermeable Endothelial Barrier in Sepsis: Clues to a Molecular Mechanism.Journal of community medicine & public health · 2024Article
- Review
- Discovery of a Promising Fluorine-18 Positron Emission Tomography Radiotracer for Imaging Sphingosine-1-Phosphate Receptor 1 in the Brain.Journal of medicinal chemistry · 2023Article
- Signal Transduction and Gene Regulation in the Endothelium.Cold Spring Harbor perspectives in medicine · 2023Review
- Renal microvascular endothelial cell responses in sepsis-induced acute kidney injury.Nature reviews. Nephrology · 2022Review
- Sepsis-induced AKI: From pathogenesis to therapeutic approaches.Frontiers in pharmacology · 2022Review
- Unlocking the Untapped Potential of Endothelial Kinase and Phosphatase Involvement in Sepsis for Drug Treatment Design.Frontiers in immunology · 2022Review
- Barrier maintenance by S1P during inflammation and sepsis.Tissue barriers · 2021Review
- The apoM/S1P Complex-A Mediator in Kidney Biology and Disease?Frontiers in medicine · 2021Review
- PET Study of Sphingosine-1-phosphate Receptor 1 Expression in Response toMolecular imaging · 2021Article
- Targeting of G-protein coupled receptors in sepsis.Pharmacology & therapeutics · 2020Review
- S1PR1-Associated Molecular Signature Predicts Survival in Patients with Sepsis.Shock (Augusta, Ga.) · 2020Article
- Determinants of Serum- and Plasma Sphingosine-1-Phosphate Concentrations in a Healthy Study Group.TH open : companion journal to thrombosis and haemostasis · 2020Article
- Frontline Science: Anti-PD-L1 protects against infection with common bacterial pathogens after burn injury.Journal of leukocyte biology · 2018Article
- Article
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5 authors at 1 institution in 1 country.
Funding
Abstract
Microvascular failure is hallmark of sepsis in humans and is recognized as a strong predictor of mortality. In the mouse subjected to cecal ligation and puncture (CLP) to induce a clinically relevant sepsis, renal microvascular permeability increases and peritubular capillary perfusion declines rapidly in the kidney leading to acute kidney injury (AKI). Sphingosine-1-phosphate (S1P) is a key regulator of microvascular endothelial function. To investigate the role of S1P in the development of microvascular permeability and peritubular capillary hypoperfusion in the kidney during CLP-induced AKI, we used a pharmacologic approach and a clinically relevant delayed dosing paradigm. Evans blue dye was used to measure renal microvascular permeability and intravital video microscopy was used to quantitate renal cortical capillary perfusion. The S1P receptor 1 (S1P1) agonist SEW2871 [5-[4-phenyl-5-(trifluoromethyl)-2-thienyl]-3-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole] and S1P2 antagonist JTE-013 [N-(2,6-dichloro-4-pyridinyl)-2-[1,3-dimethyl-4-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-hydrazinecarboxamide] were administered at the time of CLP and produced a dose-dependent but partial reduction in renal microvascular permeability at 6 hours after CLP. However, neither agent improved capillary perfusion at 6 hours. With delayed administration at 6 hours after CLP, only SEW2871 reversed microvascular permeability when measured at 18 hours. Importantly, SEW2871 also restored capillary perfusion and improved renal function. These data suggest that S1P1 and S1P2 do not regulate the early decline in renal capillary perfusion. However, later in the course of sepsis, pharmacologic stimulation of S1P1, even when delaying therapy until after injury has occurred, improves capillary and renal function, suggesting this approach should be evaluated as an adjunct therapy during sepsis.
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