ArticleAmerican journal of respiratory and critical care medicine2014
The sphingosine kinase 1/sphingosine-1-phosphate pathway in pulmonary arterial hypertension.
Article in American journal of respiratory and critical care medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
88 citing papers in PubMed, 144 citations in OpenAlex.
- G Protein-Coupled Receptor in High-Altitude Diseases: Mechanistic Insights and Therapeutic Opportunities.MedComm · 2026Review
- Metabolomic Network Analysis Reveals Reorganization of Lipid and Steroid Programs Linked to Right Ventricular-Pulmonary Vascular Function in Pulmonary Hypertension.bioRxiv : the preprint server for biology · 2026Article
- Sphingolipid Signaling in Vascular Smooth Muscle Cells during Development and Diseases.JMA journal · 2026Review
- Sphingosine-1-phosphate induces pulmonary artery smooth muscle cell proliferation, migration and pulmonary arterial remodeling by modulating sonic hedgehog signaling effector FoxM1.Chinese medical journal · 2026Article
- Targeting Leishmania donovani Sphingosine Kinase 1 using PF-543 enhances immune response and limits parasite load.PLoS neglected tropical diseases · 2026Article
- Sphingosine kinase 1 is integral for elastin deficiency-induced arterial hypermuscularization.Nature cardiovascular research · 2026Article
- Roles of Lipid Metabolism in Pulmonary Hypertension: Friend or Foe?Biomolecules · 2025Review
- The mitochondrial unfolded protein response and metabolic reprogramming promote PASMC proliferation in response to sphingosine kinase-1/sphingosine-1-phosphate signaling.bioRxiv : the preprint server for biology · 2025Article
- Molecular Pathogenesis of Connective Tissue Disease-Associated Pulmonary Arterial Hypertension: A Narrative Review.Biomolecules · 2025Review
- Observational
- Exercise improves systemic metabolism in a monocrotaline model of pulmonary hypertension.Sports medicine and health science · 2025Article
- Elucidation of Dysregulated Pathways Associated With Hypoxia in Oestrogen Receptor-Negative Breast Cancer.Cancer medicine · 2024Article
- Unveiling the metabolic landscape of pulmonary hypertension: insights from metabolomics.Respiratory research · 2024Review
- Review
- Multi-omics reveals the phyllosphere microbial community and material transformations in cigars.Frontiers in microbiology · 2024Article
- S1P/S1PR signaling pathway advancements in autoimmune diseases.Biomolecules & biomedicine · 2023Review
- Altered Smooth Muscle Cell Histone Acetylome by the SPHK2/S1P Axis Promotes Pulmonary Hypertension.Circulation research · 2023Article
- Acid ceramidase gene therapy ameliorates pulmonary arterial hypertension with right heart dysfunction.Respiratory research · 2023Article
- Pathophysiology and pathogenic mechanisms of pulmonary hypertension: role of membrane receptors, ion channels, and CaPhysiological reviews · 2023Review
- Pathophysiological Involvement of Mast Cells and the Lipid Mediators in Pulmonary Vascular Remodeling.International journal of molecular sciences · 2023Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
18 authors at 2 institutions in 1 country.
Funding
Abstract
rationaleSphingosine kinases (SphKs) 1 and 2 regulate the synthesis of the bioactive sphingolipid sphingosine-1-phosphate (S1P), an important lipid mediator that promotes cell proliferation, migration, and angiogenesis.
objectivesWe aimed to examine whether SphKs and their product, S1P, play a role in the development of pulmonary arterial hypertension (PAH).
methodsSphK1(-/-), SphK2(-/-), and S1P lyase heterozygous (Sgpl1(+/-)) mice, a pharmacologic SphK inhibitor (SKI2), and a S1P receptor 2 (S1PR2) antagonist (JTE013) were used in rodent models of hypoxia-mediated pulmonary hypertension (HPH). S1P levels in lung tissues from patients with PAH and pulmonary arteries (PAs) from rodent models of HPH were measured. MEASUREMENTS AND MAIN
resultsmRNA and protein levels of SphK1, but not SphK2, were significantly increased in the lungs and isolated PA smooth muscle cells (PASMCs) from patients with PAH, and in lungs of experimental rodent models of HPH. S1P levels were increased in lungs of patients with PAH and PAs from rodent models of HPH. Unlike SphK2(-/-) mice, SphK1(-/-) mice were protected against HPH, whereas Sgpl1(+/-) mice were more susceptible to HPH. Pharmacologic SphK1 and S1PR2 inhibition prevented the development of HPH in rodent models of HPH. Overexpression of SphK1 and stimulation with S1P potentially via ligation of S1PR2 promoted PASMC proliferation in vitro, whereas SphK1 deficiency inhibited PASMC proliferation.
conclusionsThe SphK1/S1P axis is a novel pathway in PAH that promotes PASMC proliferation, a major contributor to pulmonary vascular remodeling. Our results suggest that this pathway is a potential therapeutic target in PAH.
Indexed as
Identifiers
What OpenQuestion holds
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.