ArticleThe Journal of biological chemistry2008
Up-regulating sphingosine 1-phosphate receptor-2 signaling impairs chemotactic, wound-healing, and morphogenetic responses in senescent endothelial cells.
Article in The Journal of biological chemistry, 2008. 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, 56 citations in OpenAlex.
- Oxymatrine regulates SPHKS/S1P signaling pathway in diabetic retinopathy: an observational clinical cohort study.Scientific reports · 2026Observational
- Signal Transduction and Gene Regulation in the Endothelium.Cold Spring Harbor perspectives in medicine · 2023Review
- Adipokines in atherosclerosis: unraveling complex roles.Frontiers in cardiovascular medicine · 2023Review
- S1P receptor modulators and the cardiovascular autonomic nervous system in multiple sclerosis: a narrative review.Therapeutic advances in neurological disorders · 2022Review
- Inhibition of S1P Receptor 2 Attenuates Endothelial Dysfunction and Inhibits Atherogenesis in Apolipoprotein E-Deficient Mice.Journal of atherosclerosis and thrombosis · 2021Article
- Role of sphingolipids in senescence: implication in aging and age-related diseases.The Journal of clinical investigation · 2018Review
- Article
- In Development-A New Paradigm for Understanding Vascular Disease.Journal of cardiovascular pharmacology · 2017Review
- Impact of Age and Polytherapy on Fingolimod Induced Bradycardia: a Preclinical Study.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2017Article
- TGF-β/SMAD3 Pathway Stimulates Sphingosine-1 Phosphate Receptor 3 Expression: IMPLICATION OF SPHINGOSINE-1 PHOSPHATE RECEPTOR 3 IN LUNG ADENOCARCINOMA PROGRESSION.The Journal of biological chemistry · 2016Article
- Upregulation of S1P1 and Rac1 receptors in the pulmonary vasculature of nitrofen-induced congenital diaphragmatic hernia.Pediatric surgery international · 2016Article
- Impairment of Angiogenic Sphingosine Kinase-1/Sphingosine-1-Phosphate Receptors Pathway in Preeclampsia.PloS one · 2016Article
- Sphingosine-1-Phosphate Receptor-2 Antagonists: Therapeutic Potential and Potential Risks.Frontiers in pharmacology · 2016Review
- Impedance analysis of GPCR-mediated changes in endothelial barrier function: overview and fundamental considerations for stable and reproducible measurements.Pflugers Archiv : European journal of physiology · 2015Article
- Sphingosine-1-phosphate receptor subtype 2 signaling in endothelial senescence-associated functional impairments and inflammation.Current atherosclerosis reports · 2015Review
- The role of sphingosine-1-phosphate in endothelial barrier function.Biochimica et biophysica acta · 2014Review
- Sphingosine-1-phosphate receptor 2.The FEBS journal · 2013Review
- ETS-1-mediated transcriptional up-regulation of CD44 is required for sphingosine-1-phosphate receptor subtype 3-stimulated chemotaxis.The Journal of biological chemistry · 2013Article
- Sphingosine-1-phosphate receptor-2 mediated NFκB activation contributes to tumor necrosis factor-α induced VCAM-1 and ICAM-1 expression in endothelial cells.Prostaglandins & other lipid mediators · 2013Article
- Coronin 1B regulates S1P-induced human lung endothelial cell chemotaxis: role of PLD2, protein kinase C and Rac1 signal transduction.PloS one · 2013Article
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Vascular endothelial cells (ECs) have a finite lifespan when cultured in vitro and eventually enter an irreversible growth arrest state called "cellular senescence." It has been shown that sphingolipids may be involved in senescence; however, the molecular links involved are poorly understood. In this study, we investigated the signaling and functions of sphingosine 1-phosphate (S1P), a serum-borne bioactive sphingolipid, in ECs of different in vitro ages. We observed that S1P-regulated responses are significantly inhibited and the S1P(1-3) receptor subtypes are markedly increased in senescent ECs. Increased expression of S1P(1) and S1P(2) was also observed in the lesion regions of atherosclerotic endothelium, where senescent ECs have been identified in vivo. S1P-induced Akt and ERK1/2 activation were comparable between ECs of different in vitro ages; however, PTEN (phosphatase and tensin homolog deleted on chromosome 10) activity was significantly elevated and Rac activation was inhibited in senescent ECs. Rac activation and senescent-associated impairments were restored in senescent ECs by the expression of dominant-negative PTEN and by knocking down S1P(2) receptors. Furthermore, the senescent-associated impairments were induced in young ECs by the expression of S1P(2) to a level similar to that of in vitro senescence. These results indicate that the impairment of function in senescent ECs in culture is mediated by an increase in S1P signaling through S1P(2)-mediated activation of the lipid phosphatase PTEN.
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