186
Views
0
CrossRef citations to date
0
Altmetric
Review Articles

Insight into modulators of sphingosine-1-phosphate receptor and implications for cardiovascular therapeutics

, , ORCID Icon, , , & show all
Pages 300-310 | Received 26 Apr 2023, Accepted 21 Oct 2023, Published online: 06 Feb 2024

References

  • Kaminsky LA, German C, Imboden M, et al. The importance of healthy lifestyle behaviors in the prevention of cardiovascular disease. Prog Cardiovasc Dis. 2022;70:8–15. doi: 10.1016/j.pcad.2021.12.001.
  • Liu Y, Huang Y, Xu C, et al. Mitochondrial dysfunction and therapeutic perspectives in cardiovascular diseases. Int J Mol Sci. 2022;23(24):16053. doi: 10.3390/ijms232416053.
  • Aryan L, Younessi D, Zargari M, et al. The role of estrogen receptors in cardiovascular disease. IJMS. 2020;21(12):4314. doi: 10.3390/ijms21124314.
  • Lambrinoudaki I, Paschou SA, Armeni E, et al. The interplay between diabetes mellitus and menopause: clinical implications. Nat Rev Endocrinol. 2022;18(10):608–622. doi: 10.1038/s41574-022-00708-0.
  • Hill MA, Yang Y, Zhang L, et al. Insulin resistance, ­cardiovascular stiffening and cardiovascular disease. Metabolism. 2021;119:154766. doi: 10.1016/j.metabol.2021.154766.
  • Cannavo A, Liccardo D, Komici K, et al. Sphingosine kinases and sphingosine 1-phosphate receptors: signaling and actions in the cardiovascular system. Front Pharmacol. 2017;8:556. doi: 10.3389/fphar.2017.00556.
  • Bruce CR, Risis S, Babb JR, et al. Overexpression of sphingosine kinase 1 prevents ceramide accumulation and ameliorates muscle insulin resistance in high-fat diet-fed mice. Diabetes. 2012;61(12):3148–3155. doi: 10.2337/db12-0029.
  • Rapizzi E, Taddei ML, Fiaschi T, et al. Sphingosine 1-phosphate increases glucose uptake through trans-activation of insulin receptor. Cell Mol Life Sci. 2009;66(19):3207–3218. doi: 10.1007/s00018-009-0106-3.
  • Aji G, Huang Y, Ng ML, et al. Regulation of hepatic insulin signaling and glucose homeostasis by sphingosine kinase 2. Proc Natl Acad Sci U S A. 2020;117(39):24434–24442. doi: 10.1073/pnas.2007856117.
  • Qi Y, Wang W, Song Z, et al. Role of sphingosine kinase in type 2 diabetes mellitus. Front Endocrinol. 2020;11:627076. doi: 10.3389/fendo.2020.627076.
  • Wang J, Badeanlou L, Bielawski J, et al. Sphingosine kinase 1 regulates adipose proinflammatory responses and insulin resistance. Am J Physiol Endocrinol Metab. 2014;306(7):E756–E768. doi: 10.1152/ajpendo.00549.2013.
  • Cartier A, Hla T. Sphingosine 1-phosphate: lipid signaling in pathology and therapy. Science. 2019;366(6463):eaar5551. doi: 10.1126/science.aar5551.
  • Roy R, Alotaibi AA, Freedman MS. Sphingosine 1-phosphate receptor modulators for multiple sclerosis. CNS Drugs. 2021;35(4):385–402. doi: 10.1007/s40263-021-00798-w.
  • Chen H, Wang J, Zhang C, et al. Sphingosine 1-phosphate receptor, a new therapeutic direction in different diseases. Biomed Pharmacother. 2022;153:113341. doi: 10.1016/j.biopha.2022.113341.
  • McGinley MP, Cohen JA. Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions. Lancet. 2021;398(10306):1184–1194. doi: 10.1016/S0140-6736(21)00244-0.
  • Jozefczuk E, Guzik TJ, Siedlinski M. Significance of sphingosine-1-phosphate in cardiovascular physiology and pathology. Pharmacol Res. 2020;156:104793. doi: 10.1016/j.phrs.2020.104793.
  • Kuang Y, Li X, Liu X, et al. Vascular endothelial S1pr1 ameliorates adverse cardiac remodelling via stimulating reparative macrophage proliferation after myocardial infarction. Cardiovasc Res. 2021;117(2):585–599. doi: 10.1093/cvr/cvaa046.
  • Zhang X, Chen D, Wang J, et al. Involvement of sphingosine-1-phosphate receptors 2/3 in IR-induced sudden cardiac death. Heart Vessels. 2019;34(6):1052–1063. doi: 10.1007/s00380-018-01323-8.
  • Wang X, Li M, Yu Y, et al. FTY720 alleviates coxsackievirus B3-induced myocarditis and inhibits viral replication through regulating sphingosine 1-phosphate receptors and AKT/caspase-3 pathways. J Cell Physiol. 2019;234(10):18029–18040. doi: 10.1002/jcp.28434.
  • Di Lorenzo A. Sphingosine-1-phosphate receptor-1 (S1PR1) signalling: the homeostatic pathway of the heart. Cardiovasc Res. 2021;117(2):357–359. doi: 10.1093/cvr/cvaa224.
  • Roggeri A, Schepers M, Tiane A, et al. Sphingosine-1-phosphate receptor modulators and oligodendroglial cells: beyond immunomodulation. Int J Mol Sci. 2020;21(20):7537. doi: 10.3390/ijms21207537.
  • Xiong Y, Hla T. S1P control of endothelial integrity. Curr Top Microbiol Immunol. 2014;378:85–105. doi: 10.1007/978-3-319-05879-5_4.
  • X L, H G, C R, et al. Critical role of mitogen-inducible gene 6 in restraining endothelial cell permeability to maintain vascular homeostasis. J Cell Commun Signal. 2022;17(1):167. https://pubmed.ncbi.nlm.nih.gov/36284029/. doi: 10.1007/s12079-022-00709-8.
  • Qiu Y, Shen J, Jiang W, et al. Sphingosine 1-phosphate and its regulatory role in vascular endothelial cells. Histol Histopathol. 2022;37:213–225. doi: 10.14670/HH-18-428.
  • Balaji Ragunathrao VA, Anwar M, Akhter MZ, et al. Sphingosine-1-phosphate receptor 1 activity promotes tumor growth by amplifying VEGF-VEGFR2 angiogenic signaling. Cell Rep. 2019;29(11):3472.e4–3487.e4. doi: 10.1016/j.celrep.2019.11.036.
  • Cantalupo A, Gargiulo A, Dautaj E, et al. S1PR1 (sphingosine-1-phosphate receptor 1) signaling regulates blood flow and pressure. Hypertension. 2017;70(2):426–434. doi: 10.1161/HYPERTENSIONAHA.117.09088.
  • Reinhard NR, Mastop M, Yin T, et al. The balance between Gαi-Cdc42/rac and Gα12/13-RhoA pathways determines endothelial barrier regulation by sphingosine-1-phosphate. Mol Biol Cell. 2017;28(23):3371–3382. doi: 10.1091/mbc.E17-03-0136.
  • K P, van B M, G A, et al. Sphingosine-1-phosphate receptor 1 regulates cardiac function by modulating Ca2+ sensitivity and Na+/H + exchange and mediates protection by ischemic preconditioning. JAHA. 2016;5:e003393. https://pubmed.ncbi.nlm.nih.gov/27207969/.
  • Ye H, Zhang Y, Huang Y, et al. Bivalirudin attenuates Thrombin-Induced endothelial hyperpermeability via S1P/S1PR2 category: original articles. Front Pharmacol. 2021;12:721200. doi: 10.3389/fphar.2021.721200.
  • Ganbaatar B, Fukuda D, Shinohara M, et al. Inhibition of S1P receptor 2 attenuates endothelial dysfunction and inhibits atherogenesis in apolipoprotein E-Deficient mice. J Atheroscler Thromb. 2021;28(6):630–642. doi: 10.5551/jat.54916.
  • Wang X, Chen S, Xiang H, et al. S1PR2/RhoA/ROCK1 pathway promotes inflammatory bowel disease by inducing intestinal vascular endothelial barrier damage and M1 macrophage polarization. Biochem Pharmacol. 2022;201:115077. doi: 10.1016/j.bcp.2022.115077.
  • Ouyang J, Shu Z, Chen S, et al. The role of sphingosine 1-phosphate and its receptors in cardiovascular diseases. J Cell Mol Med. 2020;24(18):10290–10301. doi: 10.1111/jcmm.15744.
  • Oo ML, Chang S-H, Thangada S, et al. Engagement of S1P1-degradative mechanisms leads to vascular leak in mice. J Clin Invest. 2011;121(6):2290–2300. doi: 10.1172/JCI45403.
  • Del Galdo S, Vettel C, Heringdorf DMZ, et al. The activation of RhoC in vascular endothelial cells is required for the S1P receptor type 2-induced inhibition of angiogenesis. Cell Signal. 2013;25(12):2478–2484. doi: 10.1016/j.cellsig.2013.08.017.
  • Olivera A, Rivera J. An emerging role for the lipid mediator sphingosine-1-phosphate in mast cell effector function and allergic disease. Adv Exp Med Biol. 2011;716:123–142. doi: 10.1007/978-1-4419-9533-9_8.
  • Adada M, Canals D, Hannun YA, et al. Sphingosine-1-phosphate receptor 2. Febs J. 2013;280(24):6354–6366. doi: 10.1111/febs.12446.
  • Wang Y, Chen D, Zhang Y, et al. Novel adipokine, FAM19A5, inhibits neointima formation after injury through sphingosine-1-phosphate receptor 2. Circulation. 2018;138(1):48–63. doi: 10.1161/CIRCULATIONAHA.117.032398.
  • Fan X, Liu L, Shi Y, et al. Recent advances of the function of sphingosine 1-phosphate (S1P) receptor S1P3. J Cell Physiol. 2021;236(3):1564–1578. doi: 10.1002/jcp.29958.
  • Li Q, Li Y, Lei C, et al. Sphingosine-1-phosphate receptor 3 signaling. Clin Chim Acta. 2021;519:32–39. doi: 10.1016/j.cca.2021.03.025.
  • Intapad S. Sphingosine-1-phosphate signaling in blood pressure regulation. Am J Physiol Renal Physiol. 2019;317(3):F638–F640. doi: 10.1152/ajprenal.00572.2018.
  • Proia RL, Hla T. Emerging biology of sphingosine-1-phosphate: its role in pathogenesis and therapy. J Clin Invest. 2015;125(4):1379–1387. doi: 10.1172/JCI76369.
  • Olesch C, Ringel C, Brüne B, et al. Beyond immune cell migration: the emerging role of the sphingosine-1-phosphate receptor S1PR4 as a modulator of innate immune cell activation. Mediators Inflamm. 2017;2017:6059203–6059212. doi: 10.1155/2017/6059203.
  • Wang W, Graeler MH, Goetzl EJ. Type 4 sphingosine 1-phosphate G protein-coupled receptor (S1P4) transduces S1P effects on T cell proliferation and cytokine secretion without signaling migration. Faseb J. 2005;19(12):1731–1733. doi: 10.1096/fj.05-3730fje.
  • Hansen L, Lohfink N, Vutukuri R, et al. Endothelial sphingosine-1-phosphate receptor 4 regulates blood-brain barrier permeability and promotes a homeostatic endothelial phenotype. J Neurosci. 2022;42(10):1908–1929. doi: 10.1523/JNEUROSCI.0188-21.2021.
  • Behrangi N, Heinig L, Frintrop L, et al. Siponimod ameliorates metabolic oligodendrocyte injury via the sphingosine-1 phosphate receptor 5. Proc Natl Acad Sci U S A. 2022;119:e2204509119. doi: 10.1073/pnas.2204509119.
  • Aoki M, Aoki H, Ramanathan R, et al. Sphingosine-1-phosphate signaling in immune cells and inflammation: roles and therapeutic potential. Mediators Inflamm. 2016;2016:8606878. doi: 10.1155/2016/8606878.
  • Hunter SF, Bowen JD, Reder AT. The direct effects of fingolimod in the Central nervous system: implications for relapsing multiple sclerosis. CNS Drugs. 2016;30:135–147. https://pubmed.ncbi.nlm.nih.gov/26715391/
  • Drouillard A, Mathieu A-L, Marçais A, et al. S1PR5 is essential for human natural killer cell migration toward sphingosine-1 phosphate. J Allergy Clin Immunol. 2018;141(6):2265.e1–2268.e1. doi: 10.1016/j.jaci.2017.11.022.
  • Scott LJ. Fingolimod: a review of its use in the management of relapsing-remitting multiple sclerosis. CNS Drugs. 2011;25(8):673–698. doi: 10.2165/11207350-000000000-00000.
  • Huwiler A, Zangemeister-Wittke U. The sphingosine 1-phosphate receptor modulator fingolimod as a therapeutic agent: recent findings and new perspectives. Pharmacol Ther. 2018;185:34–49. doi: 10.1016/j.pharmthera.2017.11.001.
  • Adachi K, Kohara T, Nakao N, et al. Design, synthesis, and structure-activity relationships of 2-substituted-2-amino-1,3-propanediols: discovery of a novel immunosuppressant, FTY720. Bioorganic Med Chem Lett. 1995;5(8):853–856. http://www.sciencedirect.com/science/article/pii/0960894X9500127F. doi: 10.1016/0960-894X(95)00127-F.
  • Berdyshev EV, Gorshkova I, Skobeleva A, et al. FTY720 inhibits ceramide synthases and up-regulates dihydrosphingosine 1-phosphate formation in human lung endothelial cells. J Biol Chem. 2009;284(9):5467–5477. doi: 10.1074/jbc.M805186200.
  • Allam RM, Al-Abd AM, Khedr A, et al. Fingolimod interrupts the cross talk between estrogen metabolism and sphingolipid metabolism within prostate cancer cells. Toxicol Lett. 2018;291:77–85. doi: 10.1016/j.toxlet.2018.04.008.
  • Barry B, Erwin AA, Stevens J, et al. Fingolimod rebound: a review of the clinical experience and management considerations. Neurol Ther. 2019;8(2):241–250. doi: 10.1007/s40120-019-00160-9.
  • Brait VH, Tarrasón G, Gavaldà A, et al. Selective sphingosine 1-phosphate receptor 1 agonist is protective against ischemia/reperfusion in mice. Stroke. 2016;47(12):3053–3056. doi: 10.1161/STROKEAHA.116.015371.
  • Ren M, Han M, Wei X, et al. FTY720 attenuates 6-OHDA-Associated dopaminergic degeneration in cellular and mouse parkinsonian models. Neurochem Res. 2017;42(2):686–696. doi: 10.1007/s11064-016-2125-4.
  • Zhang L, Sui R, Zhang L. Fingolimod protects against cerebral ischemia reperfusion injury in rats by reducing inflammatory cytokines and inhibiting the activation of p38 MAPK and NF-κB signaling pathways. Neurosci Lett. 2022;771:136413. doi: 10.1016/j.neulet.2021.136413.
  • Tsunemi S, Iwasaki T, Kitano S, et al. Effects of the novel immunosuppressant FTY720 in a murine rheumatoid arthritis model. Clin Immunol. 2010;136(2):197–204. doi: 10.1016/j.clim.2010.03.428.
  • Szymiczek A, Pastorino S, Larson D, et al. FTY720 inhibits mesothelioma growth in vitro and in a syngeneic mouse model. J Transl Med. 2017;15(1):58. doi: 10.1186/s12967-017-1158-z.
  • Zhao M, Yang C, Chai S, et al. Curcumol and FTY720 synergistically induce apoptosis and differentiation in chronic myelomonocytic leukemia via multiple signaling pathways. Phytother Res. 2021;35(4):2157–2170. doi: 10.1002/ptr.6968.
  • Forrest M, Sun S-Y, Hajdu R, et al. Immune cell regulation and cardiovascular effects of sphingosine 1-phosphate receptor agonists in rodents are mediated via distinct receptor subtypes. J Pharmacol Exp Ther. 2004;309(2):758–768. doi: 10.1124/jpet.103.062828.
  • Pan S, Gray NS, Gao W, et al. Discovery of BAF312 (siponimod), a potent and selective S1P receptor modulator. ACS Med Chem Lett. 2013;4(3):333–337. doi: 10.1021/ml300396r.
  • Al-Salama ZT. Siponimod: first global approval. Drugs. 2019;79(9):1009–1015. doi: 10.1007/s40265-019-01140-x.
  • Colombo E, Bassani C, De Angelis A, et al. Siponimod (BAF312) activates Nrf2 while hampering NFκB in human astrocytes, and protects from Astrocyte-Induced neurodegeneration. Front Immunol. 2020;11:635. doi: 10.3389/fimmu.2020.00635.
  • Spampinato SF, Merlo S, Sano Y, et al. Protective effect of the sphingosine-1 phosphate receptor agonist siponimod on disrupted blood brain barrier function. Biochem Pharmacol. 2021;186:114465. doi: 10.1016/j.bcp.2021.114465.
  • Bobinger T, Manaenko A, Burkardt P, et al. Siponimod (BAF-312) attenuates perihemorrhagic edema and improves survival in experimental intracerebral hemorrhage. Stroke. 2019;50(11):3246–3254. doi: 10.1161/STROKEAHA.119.027134.
  • Lamb YN. Ozanimod: first approval. Drugs. 2020;80(8):841–848. doi: 10.1007/s40265-020-01319-7.
  • Argollo M, Furfaro F, Gilardi D, et al. Modulation of sphingosine-1-phosphate in ulcerative colitis. Expert Opin Biol Ther. 2020;20(4):413–420. doi: 10.1080/14712598.2020.1732919.
  • Asakura T, Ishii M, Namkoong H, et al. Sphingosine 1-phosphate receptor modulator ONO-4641 stimulates CD11b + Gr-1+ cell expansion and inhibits lymphocyte infiltration in the lungs to ameliorate murine pulmonary emphysema. Mucosal Immunol. 2018;11(6):1606–1620. doi: 10.1038/s41385-018-0077-5.
  • Komiya T, Gohda M, Shioya H, et al. Sphingosine 1-phosphate receptor modulator ONO-4641 regulates trafficking of T lymphocytes and hematopoietic stem cells and alleviates immune-mediated aplastic anemia in a mouse model. J Pharmacol Exp Ther. 2021;376(2):250–260. doi: 10.1124/jpet.120.000277.
  • Imeri F, Stepanovska Tanturovska B, Zivkovic A, et al. Novel compounds with dual S1P receptor agonist and histamine H3 receptor antagonist activities act protective in a mouse model of multiple sclerosis. Neuropharmacology. 2021;186:108464. doi: 10.1016/j.neuropharm.2021.108464.
  • Sanna MG, Liao J, Jo E, et al. Sphingosine 1-phosphate (S1P) receptor subtypes S1P1 and S1P3, respectively, regulate lymphocyte recirculation and heart rate. J Biol Chem. 2004;279(14):13839–13848. doi: 10.1074/jbc.M311743200.
  • Lien Y-H, Yong K-C, Cho C, et al. S1P(1)-selective agonist, SEW2871, ameliorates ischemic acute renal failure. Kidney Int. 2006;69(9):1601–1608. doi: 10.1038/sj.ki.5000360.
  • Dong J, Wang H, Zhao J, et al. SEW2871 protects from experimental colitis through reduced epithelial cell apoptosis and improved barrier function in interleukin-10 gene-deficient mice. Immunol Res. 2015;61(3):303–311. doi: 10.1007/s12026-015-8625-5.
  • Ito T, Kuriyama N, Kato H, et al. Sinusoidal protection by sphingosine-1-phosphate receptor 1 agonist in liver ischemia-reperfusion injury. J Surg Res. 2018;222:139–152. doi: 10.1016/j.jss.2017.09.048.
  • Marmonti E, Savage H, Zhang A, et al. Modulating sphingosine-1-phosphate receptors to improve chemotherapy efficacy against Ewing sarcoma. Int J Cancer. 2020;147(4):1206–1214. doi: 10.1002/ijc.32862.
  • Yang T, Wang X, Zhou Y, et al. SEW2871 attenuates ANIT-induced hepatotoxicity by protecting liver barrier function via sphingosine 1-phosphate receptor-1-mediated AMPK signaling pathway. Cell Biol Toxicol. 2021;37(4):595–609. doi: 10.1007/s10565-020-09567-9.
  • Shimizu H, Takahashi M, Kaneko T, et al. KRP-203, a novel synthetic immunosuppressant, prolongs graft survival and attenuates chronic rejection in rat skin and heart allografts. Circulation. 2005;111(2):222–229. doi: 10.1161/01.CIR.0000152101.41037.AB.
  • Fujishiro J, Kudou S, Iwai S, et al. Use of sphingosine-1-phosphate 1 receptor agonist, KRP-203, in combination with a subtherapeutic dose of cyclosporine a for rat renal transplantation. Transplantation. 2006;82(6):804–812. doi: 10.1097/01.tp.0000232687.78242.cd.
  • Khattar M, Deng R, Kahan BD, et al. Novel sphingosine-1-phosphate receptor modulator KRP203 combined with locally delivered regulatory T cells induces permanent acceptance of pancreatic islet allografts. Transplantation. 2013;95(7):919–927. doi: 10.1097/TP.0b013e3182842396.
  • Song J, Matsuda C, Kai Y, et al. A novel sphingosine 1-phosphate receptor agonist, 2-amino-2-propanediol hydrochloride (KRP-203), regulates chronic colitis in interleukin-10 gene-deficient mice. J Pharmacol Exp Ther. 2008;324(1):276–283. doi: 10.1124/jpet.106.119172.
  • Bolli MH, Abele S, Binkert C, et al. 2-imino-thiazolidin-4-one derivatives as potent, orally active S1P1 receptor agonists. J Med Chem. 2010;53(10):4198–4211. doi: 10.1021/jm100181s.
  • Markham A. Ponesimod: first approval. Drugs. 2021;81(8):957–962. doi: 10.1007/s40265-021-01523-z.
  • Baldin E, Lugaresi A. Ponesimod for the treatment of relapsing multiple sclerosis. Expert Opin Pharmacother. 2020;21(16):1955–1964. doi: 10.1080/14656566.2020.1799977.
  • Zhang L, Guo K, Zhou J, et al. Ponesimod protects against neuronal death by suppressing the activation of A1 astrocytes in early brain injury after experimental subarachnoid hemorrhage. J Neurochem. 2021;158(4):880–897. doi: 10.1111/jnc.15457.
  • Hou H, Sun Y, Miao J, et al. Ponesimod modulates the Th1/Th17/treg cell balance and ameliorates disease in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2021;356:577583. doi: 10.1016/j.jneuroim.2021.577583.
  • Li H, Zhou X, Li Y, et al. The selective sphingosine 1-phosphate receptor 1 modulator RP101075 improves microvascular circulation after cerebrovascular thrombosis. Faseb J. 2019;33(10):10935–10941. doi: 10.1096/fj.201900282R.
  • Sun N, Shen Y, Han W, et al. Selective sphingosine-1-phosphate receptor 1 modulation attenuates experimental intracerebral hemorrhage. Stroke. 2016;47(7):1899–1906. doi: 10.1161/STROKEAHA.115.012236.
  • Stepanovska B, Zivkovic A, Enzmann G, et al. Morpholino analogues of fingolimod as novel and selective S1P1 ligands with in vivo efficacy in a mouse model of experimental antigen-induced encephalomyelitis. Int J Mol Sci. 2020;21(18):6463. doi: 10.3390/ijms21186463.
  • Stepanovska Tanturovska B, Zivkovic A, Imeri F, et al. ST-2191, an anellated bismorpholino derivative of Oxy-Fingolimod, shows selective S1P1 agonist and functional antagonist potency in vitro and in vivo. Molecules. 2021;26(17):5134. doi: 10.3390/molecules26175134.
  • Poirier B, Briand V, Kadereit D, et al. A G protein-biased S1P1 agonist, SAR247799, protects endothelial cells without affecting lymphocyte numbers. Sci Signal. 2020;13(634):eaax8050. doi: 10.1126/scisignal.aax8050.
  • Evaristi MF, Poirier B, Chénedé X, et al. A G-protein-biased S1P1 agonist, SAR247799, improved LVH and diastolic function in a rat model of metabolic syndrome. PLOS One. 2022;17(1):e0257929. doi: 10.1371/journal.pone.0257929.
  • Bergougnan L, Andersen G, Plum-Mörschel L, et al. Endothelial-protective effects of a G-protein-biased sphingosine-1 phosphate receptor-1 agonist, SAR247799, in type-2 diabetes rats and a randomized placebo-controlled patient trial. Br J Clin Pharmacol. 2021;87(5):2303–2320. doi: 10.1111/bcp.14632.
  • Satsu H, Schaeffer M-T, Guerrero M, et al. A sphingosine 1-phosphate receptor 2 selective allosteric agonist. Bioorg Med Chem. 2013;21(17):5373–5382. doi: 10.1016/j.bmc.2013.06.012.
  • Weske S, Vaidya M, von Wnuck Lipinski K, et al. Agonist-induced activation of the S1P receptor 2 constitutes a novel osteoanabolic therapy for the treatment of osteoporosis in mice. Bone. 2019;125:1–7. doi: 10.1016/j.bone.2019.04.015.
  • Kang J, Lee J-H, Im D-S. Topical application of S1P2 antagonist JTE-013 attenuates 2,4-Dinitrochlorobenzene-Induced atopic dermatitis in mice. Biomol Ther. 2020;28(6):537–541. doi: 10.4062/biomolther.2020.036.
  • Xu Q, Chen J, Zhu Y, et al. JTE-013 alleviates inflammatory injury and endothelial dysfunction induced by sepsis in vivo and in vitro. J Surg Res. 2021;265:323–332. doi: 10.1016/j.jss.2021.03.006.
  • Yang J, Tang X, Li B, et al. Sphingosine 1-phosphate receptor 2 mediated early stages of pancreatic and systemic inflammatory responses via NF-kappa B activation in acute pancreatitis. Cell Commun Signal. 2022;20(1):157. doi: 10.1186/s12964-022-00971-8.
  • Tang H-B, Jiang X-J, Wang C, et al. S1P/S1PR3 signaling mediated proliferation of pericytes via ras/pERK pathway and CAY10444 had beneficial effects on spinal cord injury. Biochem Biophys Res Commun. 2018;498(4):830–836. doi: 10.1016/j.bbrc.2018.03.065.
  • Gaire BP, Song M-R, Choi JW. Sphingosine 1-phosphate receptor subtype 3 (S1P3) contributes to brain injury after transient focal cerebral ischemia via modulating microglial activation and their M1 polarization. J Neuroinflammation. 2018;15(1):284. doi: 10.1186/s12974-018-1323-1.
  • Hu Y, Yang C, Shen G, et al. Hyperglycemia-Triggered sphingosine-1-phosphate and sphingosine-1-phosphate receptor 3 signaling worsens liver ischemia/reperfusion injury by regulating M1/M2 polarization. Liver Transpl. 2019;25(7):1074–1090. doi: 10.1002/lt.25470.
  • Xu D, Gao Q, Wang F, et al. Sphingosine-1-phosphate receptor 3 is implicated in BBB injury via the CCL2-CCR2 axis following acute intracerebral hemorrhage. CNS Neurosci Ther. 2021;27(6):674–686. doi: 10.1111/cns.13626.
  • Fan X, Chen H, Xu C, et al. S1PR3, as a core protein related to ischemic stroke, is involved in the regulation of blood-brain barrier damage. Front Pharmacol. 2022;13:834948. doi: 10.3389/fphar.2022.834948.
  • Nofer J-R, Bot M, Brodde M, et al. FTY720, a synthetic sphingosine 1 phosphate analogue, inhibits development of atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation. 2007;115(4):501–508. doi: 10.1161/CIRCULATIONAHA.106.641407.
  • Keul P, Tölle M, Lucke S, et al. The sphingosine-1-phosphate analogue FTY720 reduces atherosclerosis in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol. 2007;27(3):607–613. doi: 10.1161/01.ATV.0000254679.42583.88.
  • Gonzalez L, Qian AS, Tahir U, et al. Sphingosine-1-phosphate receptor 1, expressed in myeloid cells, slows Diet-Induced atherosclerosis and protects against macrophage apoptosis in ldlr KO mice. Int J Mol Sci. 2017;18(12):2721. doi: 10.3390/ijms18122721.
  • Santos-Gallego CG, Vahl TP, Goliasch G, et al. Sphingosine-1-phosphate receptor agonist fingolimod increases myocardial salvage and decreases adverse postinfarction left ventricular remodeling in a porcine model of ischemia/reperfusion. Circulation. 2016;133(10):954–966. doi: 10.1161/CIRCULATIONAHA.115.012427.
  • Egom EEA, Ke Y, Musa H, et al. FTY720 prevents ischemia/reperfusion injury-associated arrhythmias in an ex vivo rat heart model via activation of Pak1/akt signaling. J Mol Cell Cardiol. 2010;48(2):406–414. doi: 10.1016/j.yjmcc.2009.10.009.
  • Means CK, Xiao C-Y, Li Z, et al. Sphingosine 1-phosphate S1P2 and S1P3 receptor-mediated akt activation protects against in vivo myocardial ischemia-reperfusion injury. Am J Physiol Heart Circ Physiol. 2007;292(6):H2944–2951. doi: 10.1152/ajpheart.01331.2006.
  • Yung BS, Brand CS, Xiang SY, et al. Selective coupling of the S1P3 receptor subtype to S1P-mediated RhoA activation and cardio protection. J Mol Cell Cardiol. 2017;103:1–10. doi: 10.1016/j.yjmcc.2016.12.008.
  • Ng ML, Wadham C, Sukocheva OA. The role of sphingolipid signalling in diabetes‑associated pathologies (review). Int J Mol Med. 2017;39(2):243–252. doi: 10.3892/ijmm.2017.2855.
  • Sukocheva OA, Wang L, Albanese N, et al. Sphingosine kinase transmits estrogen signaling in human breast cancer cells. Mol Endocrinol. 2003;17(10):2002–2012. doi: 10.1210/me.2003-0119.
  • Sukocheva O, Wadham C, Gamble J, et al. Sphingosine-1-phosphate receptor 1 transmits estrogens’ effects in endothelial cells. Steroids. 2015;104:237–245. doi: 10.1016/j.steroids.2015.10.009.
  • Xu H, Jin Y, Ni H, et al. Sphingosine-1-phosphate receptor agonist, FTY720, restores coronary flow reserve in diabetic rats. Circ J. 2014;78(12):2979–2986. doi: 10.1253/circj.cj-14-0521.
  • Liu W, Liu B, Liu S, et al. Sphingosine-1-phosphate receptor 2 mediates endothelial cells dysfunction by PI3K-Akt pathway under high glucose condition. Eur J Pharmacol. 2016;776:19–25. doi: 10.1016/j.ejphar.2016.02.056.
  • Ogawa R, Takahashi M, Hirose S-I, et al. A novel sphingosine-1-phosphate receptor agonist KRP-203 attenuates rat autoimmune myocarditis. Biochem Biophys Res Commun. 2007;361(3):621–628. doi: 10.1016/j.bbrc.2007.07.061.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.