ArticleAmerican journal of respiratory cell and molecular biology2010
Prolonged exposure to sphingosine 1-phosphate receptor-1 agonists exacerbates vascular leak, fibrosis, and mortality after lung injury.
Article in American journal of respiratory cell and molecular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers.
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Who cites it
96 citing papers in PubMed, 155 citations in OpenAlex.
- First-in-human study of the safety, tolerability, pharmacokinetics and pharmacodynamics of single and multiple oral doses of SAR247799, a selective G-protein-biased sphingosine-1 phosphate receptor-1 agonist for endothelial protection.British journal of clinical pharmacology · 2021Trial
- Mechanistic insights and therapeutic potential of sphingosine‑1‑phosphate in the development of pulmonary fibrosis (Review).Molecular medicine reports · 2026Review
- Enhancing Lung Recovery: Inhaled Poly(lactic-ACS nano · 2025Article
- The endothelium: gatekeeper to lung ischemia-reperfusion injury.Respiratory research · 2024Review
- Molecular Imaging of Fibrosis in Benign Diseases: An Overview of the State of the Art.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Augmentation of Endothelial S1PR1 Attenuates Postviral Pulmonary Fibrosis.American journal of respiratory cell and molecular biology · 2024Article
- The effect of gut microbiome and plasma metabolome on systemic sclerosis: a bidirectional two-sample Mendelian randomization study.Frontiers in microbiology · 2024Article
- S1P/S1PR signaling pathway advancements in autoimmune diseases.Biomolecules & biomedicine · 2023Review
- Promising Therapeutic Treatments for Cardiac Fibrosis: Herbal Plants and Their Extracts.Cardiology and therapy · 2023Review
- Sphingosine-1-Phosphate as Lung and Cardiac Vasculature Protecting Agent in SARS-CoV-2 Infection.International journal of molecular sciences · 2023Article
- Lipid metabolism in idiopathic pulmonary fibrosis: From pathogenesis to therapy.Journal of molecular medicine (Berlin, Germany) · 2023Review
- The Role of Sphingolipids in Regulating Vascular Permeability in Idiopathic Pulmonary Fibrosis.Biomedicines · 2023Review
- Rationale for Use of Sphingosine-1-Phosphate Receptor Modulators in COVID-19 Patients: Overview of Scientific Evidence.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Review
- S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung.Acta pharmaceutica Sinica. B · 2023Article
- The matricellular protein CCN3 supports lung endothelial homeostasis and function.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Significance of Pulmonary Endothelial Injury and the Role of Cyclooxygenase-2 and Prostanoid Signaling.Bioengineering (Basel, Switzerland) · 2023Review
- [European journal of nuclear medicine and molecular imaging · 2022Article
- Selective sphingosine-1-phosphate receptor 1 modulator attenuates blood-brain barrier disruption following traumatic brain injury by inhibiting vesicular transcytosis.Fluids and barriers of the CNS · 2022Article
- Sphingosine 1-phosphate receptor-targeted therapeutics in rheumatic diseases.Nature reviews. Rheumatology · 2022Review
- [Research advances of the roles of sphingosine-1-phosphate in acute lung injury].Zhonghua shao shang yu chuang mian xiu fu za zhi · 2022Review
36 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Sphingosine 1-phosphate (S1P) is a key endogenous regulator of the response to lung injury, maintaining endothelial barrier integrity through interaction with one of its receptors, S1P(1). The short-term administration of S1P or S1P(1) receptor agonists enhances endothelial monolayer barrier function in vitro, and attenuates injury-induced vascular leak in the lung and other organ systems in vivo. Although S1P(1) agonists bind to and activate S1P(1), several of these agents also induce receptor internalization and degradation, and may therefore act as functional antagonists of S1P(1) after extended exposure. Here we report on the effects of prolonged exposure to these agents in bleomycin-induced lung injury. We demonstrate that repeated administration of S1P(1) agonists dramatically worsened lung injury after bleomycin challenge, as manifested by increased vascular leak and mortality. Consistent with these results, prolonged exposure to S1P(1) agonists in vitro eliminated the ability of endothelial cell monolayers to respond appropriately to the barrier-protective effects of S1P, indicating a loss of normal S1P-S1P(1) signaling. As bleomycin-induced lung injury progressed, continued exposure to S1P(1) agonists also resulted in increased pulmonary fibrosis. These data indicate that S1P(1) agonists can act as functional antagonists of S1P(1) on endothelial cells in vivo, which should be considered in developing these agents as therapies for vascular leak syndromes. Our findings also support the hypothesis that vascular leak is an important component of the fibrogenic response to lung injury, and suggest that targeting the S1P-S1P(1) pathway may also be an effective therapeutic strategy for fibrotic lung diseases.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.