MeSH term | MeSH ID | Detail |
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Farber Lipogranulomatosis | D055577 | 1 associated lipids |
Sphingosine 1-phosphate is a lipid of Sphingolipids (SP) class. Sphingosine 1-phosphate is associated with abnormalities such as Infection, Painful Bladder Syndrome, Atherosclerosis, Hyperglycemia and Rheumatoid Arthritis. The involved functions are known as Phosphorylation, Regulation, enzyme activity, Energy Absorption and Vascular Permeability. Sphingosine 1-phosphate often locates in Endothelium, Tissue membrane, Vascular System, Protoplasm and Microfilaments. The associated genes with Sphingosine 1-phosphate are MBTPS1 gene, FBXL15 gene, TEK gene, NTRK1 gene and Gene Family. The related lipids are Promega, Lipopolysaccharides, lysophosphatidic acid, Lysophosphatidylcholines and Lysophospholipids. The related experimental models are Knock-out, Mouse Model, Transgenic Model, Disease model and Experimental Autoimmune Encephalomyelitis.
To understand associated biological information of Sphingosine 1-phosphate, we collected biological information of abnormalities, associated pathways, cellular/molecular locations, biological functions, related genes/proteins, lipids and common seen animal/experimental models with organized paragraphs from literatures.
Sphingosine 1-phosphate is suspected in Lymphopenia, Ischemia, Infection, Atherosclerosis, Multiple Sclerosis, Asthma and other diseases in descending order of the highest number of associated sentences.
Disease | Cross reference | Weighted score | Related literature |
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We collected disease MeSH terms mapped to the references associated with Sphingosine 1-phosphate
Lipid pathways are not clear in current pathway databases. We organized associated pathways with Sphingosine 1-phosphate through full-text articles, including metabolic pathways or pathways of biological mechanisms.
Pathway name | Related literatures |
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Associated locations are in red color. Not associated locations are in black.
Location | Cross reference | Weighted score | Related literatures |
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Function | Cross reference | Weighted score | Related literatures |
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Lipid concept | Cross reference | Weighted score | Related literatures |
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Gene | Cross reference | Weighted score | Related literatures |
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Knock-out are used in the study 'Sphingosine 1-phosphate-dependent trafficking of peritoneal B cells requires functional NFkappaB-inducing kinase in stromal cells.' (Kunisawa J et al., 2008), Knock-out are used in the study 'Connective tissue growth factor (CTGF/CCN2) mediates angiogenic effect of S1P in human dermal microvascular endothelial cells.' (Markiewicz M et al., 2011), Knock-out are used in the study 'Chasing sphingosine-1-phosphate, a lipid mediator for cardiomyocyte survival.' (Yang Q, 2007), Knock-out are used in the study 'Local application of FTY720 to the lung abrogates experimental asthma by altering dendritic cell function.' (Idzko M et al., 2006) and Knock-out are used in the study 'Platelet endothelial cell adhesion molecule-1 modulates endothelial cell motility through the small G-protein Rho.' (Gratzinger D et al., 2003).
Mouse Model are used in the study 'Regulation of the micromechanical properties of pulmonary endothelium by S1P and thrombin: role of cortactin.' (Arce FT et al., 2008), Mouse Model are used in the study 'Sequential delivery of vascular endothelial growth factor and sphingosine 1-phosphate for angiogenesis.' (Tengood JE et al., 2010), Mouse Model are used in the study 'S1P(5) is required for sphingosine 1-phosphate-induced autophagy in human prostate cancer PC-3 cells.' (Chang CL et al., 2009), Mouse Model are used in the study 'Sphingosine-1-phosphate induces an antiinflammatory phenotype in macrophages.' (Hughes JE et al., 2008) and Mouse Model are used in the study 'The alliance of sphingosine-1-phosphate and its receptors in immunity.' (Rivera J et al., 2008).
Transgenic Model are used in the study 'Role for matrix metalloproteinase-2 in oxidized low-density lipoprotein-induced activation of the sphingomyelin/ceramide pathway and smooth muscle cell proliferation.' (Augé N et al., 2004), Transgenic Model are used in the study 'Sphingosine-1-phosphate antibodies as potential agents in the treatment of cancer and age-related macular degeneration.' (Sabbadini RA, 2011) and Transgenic Model are used in the study 'Still benched on its way to the bedside: sphingosine kinase 1 as an emerging target in cancer chemotherapy.' (Gault CR and Obeid LM, 2011).
Model | Cross reference | Weighted score | Related literatures |
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Authors | Title | Published | Journal | PubMed Link |
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Filipenko I et al. | Upregulation of the S1P3 receptor in metastatic breast cancer cells increases migration and invasion by induction of PGE2 and EP2/EP4 activation. | 2016 | Biochim. Biophys. Acta | pmid:27616330 |
Tsuchida J et al. | Breast cancer sphingosine-1-phosphate is associated with phospho-sphingosine kinase 1 and lymphatic metastasis. | 2016 | J. Surg. Res. | pmid:27621003 |
Ebenezer DL et al. | Targeting sphingosine-1-phosphate signaling in lung diseases. | 2016 | Pharmacol. Ther. | pmid:27621206 |
Stolwijk JA et al. | Calcium Signaling Is Dispensable for Receptor Regulation of Endothelial Barrier Function. | 2016 | J. Biol. Chem. | pmid:27624938 |
Roch L et al. | High-Resolution Expression Profiling of Peripheral Blood CD8 Cells in Patients with Multiple Sclerosis Displays Fingolimod-Induced Immune Cell Redistribution. | 2017 | Mol. Neurobiol. | pmid:27631876 |
Custódio R et al. | Characterization of secreted sphingosine-1-phosphate lyases required for virulence and intracellular survival of Burkholderia pseudomallei. | 2016 | Mol. Microbiol. | pmid:27632710 |
Kemppainen K et al. | Sphingosylphosphorylcholine regulates the Hippo signaling pathway in a dual manner. | 2016 | Cell. Signal. | pmid:27634386 |
Lepannetier S et al. | Sphingosine-1-phosphate-activated TRPC1 channel controls chemotaxis of glioblastoma cells. | 2016 | Cell Calcium | pmid:27638096 |
Scotti L et al. | Sphingosine-1-phosphate restores endothelial barrier integrity in ovarian hyperstimulation syndrome. | 2016 | Mol. Hum. Reprod. | pmid:27645281 |
Kobayashi N et al. | Fluorescence-based rapid measurement of sphingosine-1-phosphate transport activity in erythrocytes. | 2016 | J. Lipid Res. | pmid:27655910 |
Chew WS et al. | To fingolimod and beyond: The rich pipeline of drug candidates that target S1P signaling. | 2016 | Pharmacol. Res. | pmid:27663260 |
Hemdan NY et al. | Modulating sphingosine 1-phosphate signaling with DOP or FTY720 alleviates vascular and immune defects in mouse sepsis. | 2016 | Eur. J. Immunol. | pmid:27683081 |
Touat-Hamici Z et al. | Role of lipid phosphate phosphatase 3 in human aortic endothelial cell function. | 2016 | Cardiovasc. Res. | pmid:27694435 |
Morillon YM et al. | Antibody Binding to CD4 Induces Rac GTPase Activation and Alters T Cell Migration. | 2016 | J. Immunol. | pmid:27694496 |
Sánchez DI et al. | Melatonin prevents deregulation of the sphingosine kinase/sphingosine 1-phosphate signaling pathway in a mouse model of diethylnitrosamine-induced hepatocellular carcinoma. | 2017 | J. Pineal Res. | pmid:27696512 |
Åukomska A et al. | The effect of low levels of lead (Pb) in the blood on levels of sphingosine-1-phosphate (S1P) and expression of S1P receptor 1 in the brain of the rat in the perinatal period. | 2017 | Chemosphere | pmid:27697711 |
Beider K et al. | The Sphingosine-1-Phosphate Modulator FTY720 Targets Multiple Myeloma via the CXCR4/CXCL12 Pathway. | 2017 | Clin. Cancer Res. | pmid:27697999 |
Adamiak M et al. | The Involvment of Hematopoietic-Specific PLC -β2 in Homing and Engraftment of Hematopoietic Stem/Progenitor Cells. | 2016 | Stem Cell Rev | pmid:27704316 |
Wang X et al. | Sphingosine 1-Phosphate Activation of EGFR As a Novel Target for Meningitic Escherichia coli Penetration of the Blood-Brain Barrier. | 2016 | PLoS Pathog. | pmid:27711202 |
Roviezzo F et al. | Disodium cromoglycate inhibits asthma-like features induced by sphingosine-1-phosphate. | 2016 | Pharmacol. Res. | pmid:27713021 |
Ebenezer DL et al. | Epigenetic regulation of pro-inflammatory cytokine secretion by sphingosine 1-phosphate (S1P) in acute lung injury: Role of S1P lyase. | 2017 | Adv Biol Regul | pmid:27720306 |
Pal SK et al. | A phase 2 study of the sphingosine-1-phosphate antibody sonepcizumab in patients with metastatic renal cell carcinoma. | 2017 | Cancer | pmid:27727447 |
Abraham C et al. | Lessons Learned From Trials Targeting Cytokine Pathways in Patients With Inflammatory Bowel Diseases. | 2017 | Gastroenterology | pmid:27780712 |
McLean CJ et al. | Characterization of homologous sphingosine-1-phosphate lyase isoforms in the bacterial pathogen Burkholderia pseudomallei. | 2017 | J. Lipid Res. | pmid:27784725 |
González-Fernández B et al. | Inhibition of the SphK1/S1P signaling pathway by melatonin in mice with liver fibrosis and human hepatic stellate cells. | 2017 | Biofactors | pmid:27801960 |
Zhao Z et al. | Characterization of the Anticoagulant and Antithrombotic Properties of the Sphingosine 1-Phosphate Mimetic FTY720. | 2017 | Acta Haematol. | pmid:27802432 |
Zamora-Pineda J et al. | Dendritic cell sphingosine-1-phosphate lyase regulates thymic egress. | 2016 | J. Exp. Med. | pmid:27810923 |
Li S et al. | Sphk1 promotes breast epithelial cell proliferation via NF-κB-p65-mediated cyclin D1 expression. | 2016 | Oncotarget | pmid:27811358 |
Yanagida K and Hla T | Vascular and Immunobiology of the Circulatory Sphingosine 1-Phosphate Gradient. | 2017 | Annu. Rev. Physiol. | pmid:27813829 |
Chen T et al. | Sphingosine-1 phosphate promotes intestinal epithelial cell proliferation via S1PR2. | 2017 | Front Biosci (Landmark Ed) | pmid:27814635 |
Leo A et al. | The Sphingosine 1-Phosphate Signaling Pathway in Epilepsy: A Possible Role for the Immunomodulator Drug Fingolimod in Epilepsy Treatment. | 2017 | CNS Neurol Disord Drug Targets | pmid:27823573 |
Tan SF et al. | Acid ceramidase is upregulated in AML and represents a novel therapeutic target. | 2016 | Oncotarget | pmid:27825124 |
O'Sullivan S and Dev KK | Sphingosine-1-phosphate receptor therapies: Advances in clinical trials for CNS-related diseases. | 2017 | Neuropharmacology | pmid:27825807 |
Brait VH et al. | Selective Sphingosine 1-Phosphate Receptor 1 Agonist Is Protective Against Ischemia/Reperfusion in Mice. | 2016 | Stroke | pmid:27827329 |
Terashita T et al. | Administration of JTE013 abrogates experimental asthma by regulating proinflammatory cytokine production from bronchial epithelial cells. | 2016 | Respir. Res. | pmid:27829417 |
Trinh HK et al. | Exploration of the Sphingolipid Metabolite, Sphingosine-1-phosphate and Sphingosine, as Novel Biomarkers for Aspirin-exacerbated Respiratory Disease. | 2016 | Sci Rep | pmid:27830727 |
Wang R et al. | Hepatic Stellate Cell Selective Disruption of Dynamin-2 GTPase Increases Murine Fibrogenesis through Up-Regulation of Sphingosine-1 Phosphate-Induced Cell Migration. | 2017 | Am. J. Pathol. | pmid:27840081 |
Fang V et al. | Gradients of the signaling lipid S1P in lymph nodes position natural killer cells and regulate their interferon-γ response. | 2017 | Nat. Immunol. | pmid:27841869 |
Frias MA et al. | High-density lipoprotein-associated sphingosine-1-phosphate activity in heterozygous familial hypercholesterolaemia. | 2017 | Eur. J. Clin. Invest. | pmid:27861771 |
Fu P et al. | Role of Sphingosine Kinase 1 and S1P Transporter Spns2 in HGF-mediated Lamellipodia Formation in Lung Endothelium. | 2016 | J. Biol. Chem. | pmid:27864331 |
Barnawi J et al. | Reduced DNA methylation of sphingosine-1 phosphate receptor 5 in alveolar macrophages in COPD: A potential link to failed efferocytosis. | 2017 | Respirology | pmid:27868302 |
Ruiz M et al. | High-Density Lipoprotein-Associated Apolipoprotein M Limits Endothelial Inflammation by Delivering Sphingosine-1-Phosphate to the Sphingosine-1-Phosphate Receptor 1. | 2017 | Arterioscler. Thromb. Vasc. Biol. | pmid:27879252 |
Lee MH et al. | S1P in HDL promotes interaction between SR-BI and S1PR1 and activates S1PR1-mediated biological functions: calcium flux and S1PR1 internalization. | 2017 | J. Lipid Res. | pmid:27881715 |
Mao-Draayer Y et al. | The sphingosine-1-phosphate receptor: A novel therapeutic target for multiple sclerosis and other autoimmune diseases. | 2017 | Clin. Immunol. | pmid:27890706 |
Williams PA et al. | Alginate-Chitosan Hydrogels Provide a Sustained Gradient of Sphingosine-1-Phosphate for Therapeutic Angiogenesis. | 2017 | Ann Biomed Eng | pmid:27904998 |
Winkler MS et al. | Sphingosine-1-Phosphate: A Potential Biomarker and Therapeutic Target for Endothelial Dysfunction and Sepsis? | 2017 | Shock | pmid:27922551 |
Miyabe C et al. | A sphingosine 1-phosphate receptor agonist ameliorates animal model of vasculitis. | 2017 | Inflamm. Res. | pmid:27942751 |
Powell JA et al. | Targeting sphingosine kinase 1 induces MCL1-dependent cell death in acute myeloid leukemia. | 2017 | Blood | pmid:27956387 |
Soltau I et al. | Serum-Sphingosine-1-Phosphate Concentrations Are Inversely Associated with Atherosclerotic Diseases in Humans. | 2016 | PLoS ONE | pmid:27973607 |
Surya VN et al. | Sphingosine 1-phosphate receptor 1 regulates the directional migration of lymphatic endothelial cells in response to fluid shear stress. | 2016 | J R Soc Interface | pmid:27974574 |
Myśliwiec H et al. | Increase in circulating sphingosine-1-phosphate and decrease in ceramide levels in psoriatic patients. | 2017 | Arch. Dermatol. Res. | pmid:27988894 |
Contaifer D et al. | Unsupervised analysis of combined lipid and coagulation data reveals coagulopathy subtypes among dialysis patients. | 2017 | J. Lipid Res. | pmid:27993949 |
Bigaud M et al. | Pathophysiological Consequences of a Break in S1P1-Dependent Homeostasis of Vascular Permeability Revealed by S1P1 Competitive Antagonism. | 2016 | PLoS ONE | pmid:28005953 |
Al Fadel F et al. | Involvement of Sphingosine 1-Phosphate in Palmitate-Induced Non-Alcoholic Fatty Liver Disease. | 2016 | Cell. Physiol. Biochem. | pmid:28006772 |
Yung BS et al. | Selective coupling of the S1P receptor subtype to S1P-mediated RhoA activation and cardioprotection. | 2017 | J. Mol. Cell. Cardiol. | pmid:28017639 |
Ogle ME et al. | Sphingosine-1-Phosphate Receptor-3 Supports Hematopoietic Stem and Progenitor Cell Residence Within the Bone Marrow Niche. | 2017 | Stem Cells | pmid:28026131 |
Lei YC et al. | C5a/C5aR pathway is essential for up-regulating SphK1 expression through p38-MAPK activation in acute liver failure. | 2016 | World J. Gastroenterol. | pmid:28028363 |
Alqinyah M et al. | Regulator of G Protein Signaling 10 (Rgs10) Expression Is Transcriptionally Silenced in Activated Microglia by Histone Deacetylase Activity. | 2017 | Mol. Pharmacol. | pmid:28031332 |
Feuerborn R et al. | High density lipoprotein (HDL)-associated sphingosine 1-phosphate (S1P) inhibits macrophage apoptosis by stimulating STAT3 activity and survivin expression. | 2017 | Atherosclerosis | pmid:28038379 |
Silva VR et al. | Hypothalamic S1P/S1PR1 axis controls energy homeostasis in Middle-Aged Rodents: the reversal effects of physical exercise. | 2016 | Aging (Albany NY) | pmid:28039439 |
Lima S et al. | Sphingosine and Sphingosine Kinase 1 Involvement in Endocytic Membrane Trafficking. | 2017 | J. Biol. Chem. | pmid:28049734 |
van der Weyden L et al. | Genome-wide in vivo screen identifies novel host regulators of metastatic colonization. | 2017 | Nature | pmid:28052056 |
Ng ML et al. | The role of sphingolipid signalling in diabetes‑associated pathologies (Review). | 2017 | Int. J. Mol. Med. | pmid:28075451 |
Pierucci F et al. | Vitamin D protects against Aβ peptide cytotoxicity in differentiated human neuroblastoma SH- SY5Y cells: A role for S1P1/p38MAPK/ATF4 axis. | 2017 | Neuropharmacology | pmid:28077289 |
Atkinson D et al. | Sphingosine 1-phosphate lyase deficiency causes Charcot-Marie-Tooth neuropathy. | 2017 | Neurology | pmid:28077491 |
Meissner A et al. | Sphingosine-1-phosphate signalling-a key player in the pathogenesis of Angiotensin II-induced hypertension. | 2017 | Cardiovasc. Res. | pmid:28082452 |
Maiti A et al. | Metastatic triple-negative breast cancer is dependent on SphKs/S1P signaling for growth and survival. | 2017 | Cell. Signal. | pmid:28108260 |
Hsia K et al. | Sphingosine-1-phosphate improves endothelialization with reduction of thrombosis in recellularized human umbilical vein graft by inhibiting syndecan-1 shedding in vitro. | 2017 | Acta Biomater | pmid:28110073 |
Wang Y et al. | The role of sphingosine 1-phosphate receptor 2 in bile-acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice. | 2017 | Hepatology | pmid:28120434 |
Engel N et al. | Synergistic Action of Genistein and Calcitriol in Immature Osteosarcoma MG-63 Cells by SGPL1 Up-Regulation. | 2017 | PLoS ONE | pmid:28125641 |
Kurano M et al. | Involvement of CETP (Cholesteryl Ester Transfer Protein) in the Shift of Sphingosine-1-Phosphate Among Lipoproteins and in the Modulation of its Functions. | 2017 | Arterioscler. Thromb. Vasc. Biol. | pmid:28126827 |
Vishwakarma S et al. | Altered Expression of Sphingosine-1-Phosphate Metabolizing Enzymes in Oral Cancer Correlate With Clinicopathological Attributes. | 2017 | Cancer Invest. | pmid:28135860 |
Green CL et al. | The effects of graded levels of calorie restriction: IX. Global metabolomic screen reveals modulation of carnitines, sphingolipids and bile acids in the liver of C57BL/6 mice. | 2017 | Aging Cell | pmid:28139067 |
Dela Paz NG et al. | Shear stress induces Gα activation independently of G protein-coupled receptor activation in endothelial cells. | 2017 | Am. J. Physiol., Cell Physiol. | pmid:28148497 |
Moritz E et al. | Reference intervals for serum sphingosine-1-phosphate in the population-based Study of Health in Pomerania. | 2017 | Clin. Chim. Acta | pmid:28159438 |
Rojas-Canales D et al. | Local Sphingosine Kinase 1 Activity Improves Islet Transplantation. | 2017 | Diabetes | pmid:28174291 |
Moruno-Manchon JF et al. | Inhibiting sphingosine kinase 2 mitigates mutant Huntingtin-induced neurodegeneration in neuron models of Huntington disease. | 2017 | Hum. Mol. Genet. | pmid:28175299 |
Ruiz M et al. | HDL-associated ApoM is anti-apoptotic by delivering sphingosine 1-phosphate to S1P1 & S1P3 receptors on vascular endothelium. | 2017 | Lipids Health Dis | pmid:28179022 |
Ren K et al. | ApoA-I/SR-BI modulates S1P/S1PR2-mediated inflammation through the PI3K/Akt signaling pathway in HUVECs. | 2017 | J. Physiol. Biochem. | pmid:28181168 |
Janecke AR et al. | Deficiency of the sphingosine-1-phosphate lyase SGPL1 is associated with congenital nephrotic syndrome and congenital adrenal calcifications. | 2017 | Hum. Mutat. | pmid:28181337 |
Qi H et al. | Analysis of sphingolipids in human corneal fibroblasts from normal and keratoconus patients. | 2017 | J. Lipid Res. | pmid:28188148 |
Bruno M et al. | Sphingosine 1-phosphate signaling axis mediates fibroblast growth factor 2-induced proliferation and survival of murine auditory neuroblasts. | 2017 | Biochim. Biophys. Acta | pmid:28188805 |
Rieck M et al. | Ceramide synthase 2 facilitates S1P-dependent egress of thymocytes into the circulation in mice. | 2017 | Eur. J. Immunol. | pmid:28198542 |
Sun XJ et al. | Sphingosine-1-phosphate and its receptors in anti-neutrophil cytoplasmic antibody-associated vasculitis. | 2017 | Nephrol. Dial. Transplant. | pmid:28206609 |
Zeng Y | Endothelial glycocalyx as a critical signalling platform integrating the extracellular haemodynamic forces and chemical signalling. | 2017 | J. Cell. Mol. Med. | pmid:28211170 |
Lee HM et al. | Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3. | 2017 | J. Pathol. | pmid:28240350 |
Serafimidis I et al. | Pancreas lineage allocation and specification are regulated by sphingosine-1-phosphate signalling. | 2017 | PLoS Biol. | pmid:28248965 |
Su K et al. | FTY720 Attenuates Angiotensin II-Induced Podocyte Damage via Inhibiting Inflammatory Cytokines. | 2017 | Mediators Inflamm. | pmid:28270699 |
Garnero P | The Utility of Biomarkers in Osteoporosis Management. | 2017 | Mol Diagn Ther | pmid:28271451 |
Miller M et al. | Cutting Edge: Targeting Epithelial ORMDL3 Increases, Rather than Reduces, Airway Responsiveness and Is Associated with Increased Sphingosine-1-Phosphate. | 2017 | J. Immunol. | pmid:28275141 |
Li S et al. | Sphingosine-1-phosphate activates the AKT pathway to inhibit chemotherapy induced human granulosa cell apoptosis. | 2017 | Gynecol. Endocrinol. | pmid:28277139 |
Peyrin-Biroulet L et al. | Modulation of sphingosine-1-phosphate in inflammatory bowel disease. | 2017 | Autoimmun Rev | pmid:28279838 |
Nielsen OH et al. | Sphingosine-1-Phosphate Signaling in Inflammatory Bowel Disease. | 2017 | Trends Mol Med | pmid:28283249 |
Dyckman AJ | Modulators of Sphingosine-1-phosphate Pathway Biology: Recent Advances of Sphingosine-1-phosphate Receptor 1 (S1P) Agonists and Future Perspectives. | 2017 | J. Med. Chem. | pmid:28291340 |
Shirakawa H et al. | Sphingosine-1-phosphate induces Ca signaling and CXCL1 release via TRPC6 channel in astrocytes. | 2017 | Glia | pmid:28300348 |
Patmanathan SN et al. | Mechanisms of sphingosine 1-phosphate receptor signalling in cancer. | 2017 | Cell. Signal. | pmid:28302566 |
Navarrete A et al. | A metabolomic approach shows sphingosine 1-phosphate and lysophospholipids as mediators of the therapeutic effect of liver growth factor in emphysema. | 2017 | J Pharm Biomed Anal | pmid:28314215 |
Karunakaran I and van Echten-Deckert G | Sphingosine 1-phosphate - A double edged sword in the brain. | 2017 | Biochim. Biophys. Acta | pmid:28315304 |
Takahashi C et al. | Vehicle-dependent Effects of Sphingosine 1-phosphate on Plasminogen Activator Inhibitor-1 Expression. | 2017 | J. Atheroscler. Thromb. | pmid:28321011 |
Becker S et al. | Low sphingosine-1-phosphate plasma levels are predictive for increased mortality in patients with liver cirrhosis. | 2017 | PLoS ONE | pmid:28334008 |