{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSphingosine‐1‐phosphate receptor 3 (S1PR3) has emerged as a pivotal mediator in regulating inflammation and vascular barrier dynamics. Recent evidence shows that its expression is markedly upregulated in reactive astrocytes in multiple sclerosis lesions, where S1PR3 contributes to anti‐inflammatory actions within the central nervous system. In parallel, astrocytic S1PR3 is upregulated in brain metastases, where it modulates the permeability of the blood–tumor barrier through the secretion of inflammatory mediators. In endothelial cells, S1PR3 activation mediates barrier disruption in response to edemagenic agonists, promotes P‐selectin mobilization and leukocyte rolling, and even influences phospholipase activation cascades in lung epithelial cells—all factors that impact acute lung injury and vascular permeability. Moreover, promoter polymorphisms affecting S1PR3 transcription have been linked to altered plasma levels and disease severity in acute respiratory distress, underscoring its central role in inflammatory vascular regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "7"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of tumorigenesis, S1PR3 plays versatile roles that promote cancer progression and metastasis. Elevated cytoplasmic S1PR3 expression in breast cancers correlates with shorter recurrence times and poorer patient survival, while its signaling also drives expansion of cancer stem cell populations via Notch pathway activation. S1PR3 enhances invasive properties of breast epithelial cells through upregulation of matrix metalloproteinase‐9, and it participates in growth factor receptor transactivation in breast epithelial models. In addition, m6A‐dependent stabilization of S1PR3 mRNA has been shown to promote renal cell cancer tumorigenesis, and its signaling increases epidermal growth factor receptor expression via Rho kinase in lung adenocarcinoma. S1PR3 activity is further linked to the inflammatory responses observed in sepsis and to migratory signaling in nasopharyngeal carcinoma, while its amplification and interaction with intracellular adaptor proteins (EDG3/Shc3) appear to contribute to the aggressiveness of certain brain tumors and anaplastic thyroid cancers."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "8", "end_ref": "19"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nS1PR3 also contributes to pro‐fibrotic and extracellular matrix remodeling processes in various tissues. In the liver, activation of the SphK/S1P/S1PR axis—where S1PR3 plays a significant part—stimulates fibrogenic activity and promotes hepatic stellate cell migration. Similarly, in lung fibroblasts and mesenchymal stem cells, S1PR3 activation induces extracellular matrix synthesis via non‐Smad pathways and regulates collagen expression. Furthermore, in the context of radiation‐induced pulmonary fibrosis, S1PR3 mediates the epithelial–mesenchymal transition through signaling cascades that can be modulated by microRNAs, thereby linking its activity to fibrotic progression."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "20", "end_ref": "26"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, S1PR3 is integral to angiogenesis and the regulation of endothelial signaling. A synthetic peptide derived from the intracellular loop of S1PR3 replicates the receptor’s ability to stimulate Gi‐dependent MEK–ERK signaling and robust vascular sprouting, synergizing with pro‐angiogenic growth factors. In addition, S1PR3—in conjunction with S1PR1—regulates endothelial nitric oxide synthase activation to support vascular homeostasis, while its modulation in retinal pigment epithelial cells influences vascular endothelial growth factor receptor expression and choroidal neovascularization. S1PR3 also forms functional complexes with integrin β4, thereby orchestrating endothelial barrier responses in models of tissue regeneration."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "27", "end_ref": "30"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ruben Van Doorn, Jack Van Horssen, Dennis Verzijl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine 1-phosphate receptor 1 and 3 are upregulated in multiple sclerosis lesions."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Glia (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/glia.21021"}], "href": "https://doi.org/10.1002/glia.21021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20648639"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20648639"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Patrick A Singleton, Liliana Moreno-Vinasco, Saad Sammani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Attenuation of vascular permeability by methylnaltrexone: role of mOP-R and S1P3 transactivation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2007)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2006-0327OC"}], "href": "https://doi.org/10.1165/rcmb.2006-0327OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17395891"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17395891"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Brunilde Gril, Anurag N Paranjape, Stephan Woditschka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Reactive astrocytic S1P3 signaling modulates the blood-tumor barrier in brain metastases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41467-018-05030-w"}], "href": "https://doi.org/10.1038/s41467-018-05030-w"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30006619"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30006619"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Xiaoguang Sun, Patrick A Singleton, Eleftheria Letsiou, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine-1-phosphate receptor-3 is a novel biomarker in acute lung injury."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Cell Mol Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1165/rcmb.2012-0048OC"}], "href": "https://doi.org/10.1165/rcmb.2012-0048OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22771388"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22771388"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Claudia Nussbaum, Sarah Bannenberg, Petra Keul, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine-1-phosphate receptor 3 promotes leukocyte rolling by mobilizing endothelial P-selectin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2015)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms7416"}], "href": "https://doi.org/10.1038/ncomms7416"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25832730"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25832730"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Xiaoguang Sun, Shwu-Fan Ma, Michael S Wade, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Functional promoter variants in sphingosine 1-phosphate receptor 3 associate with susceptibility to sepsis-associated acute respiratory distress syndrome."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00010.2013"}], "href": "https://doi.org/10.1152/ajplung.00010.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23911438"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23911438"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Li-Yuan Chen, Grzegorz Woszczek, Sahrudaya Nagineni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Cytosolic phospholipase A2alpha activation induced by S1P is mediated by the S1P3 receptor in lung epithelial cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Physiol Lung Cell Mol Physiol (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1152/ajplung.00393.2007"}], "href": "https://doi.org/10.1152/ajplung.00393.2007"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18502815"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18502815"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Carol Watson, Jaclyn S Long, Clare Orange, et al. "}, {"type": "b", "children": [{"type": "t", "text": "High expression of sphingosine 1-phosphate receptors, S1P1 and S1P3, sphingosine kinase 1, and extracellular signal-regulated kinase-1/2 is associated with development of tamoxifen resistance in estrogen receptor-positive breast cancer patients."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Pathol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2353/ajpath.2010.100220"}], "href": "https://doi.org/10.2353/ajpath.2010.100220"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20889557"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20889557"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Naoya Hirata, Shigeru Yamada, Takuji Shoda, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine-1-phosphate promotes expansion of cancer stem cells via S1PR3 by a ligand-independent Notch activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ncomms5806"}], "href": "https://doi.org/10.1038/ncomms5806"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25254944"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25254944"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Eun-Sook Kim, Jong-Sook Kim, Sang Geon Kim, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine 1-phosphate regulates matrix metalloproteinase-9 expression and breast cell invasion through S1P3-Gαq coupling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.076794"}], "href": "https://doi.org/10.1242/jcs.076794"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21652634"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21652634"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Janet L Martin, Mike Z Lin, Eileen M McGowan, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Potentiation of growth factor signaling by insulin-like growth factor-binding protein-3 in breast epithelial cells requires sphingosine kinase activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M109.007120"}], "href": "https://doi.org/10.1074/jbc.M109.007120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19633297"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19633297"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Yufan Ying, Xueyou Ma, Jiajie Fang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EGR2-mediated regulation of m"}, {"type": "a", "children": [{"type": "t", "text": "sup"}], "href": "sup"}, {"type": "t", "text": "6"}, {"type": "a", "children": [{"type": "t", "text": "/sup"}], "href": "/sup"}, {"type": "t", "text": "A reader IGF2BP proteins drive RCC tumorigenesis and metastasis via enhancing S1PR3 mRNA stabilization."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-021-04038-3"}], "href": "https://doi.org/10.1038/s41419-021-04038-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34326314"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34326314"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Andrew Hsu, Wenliang Zhang, Jen-Fu Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine-1-phosphate receptor-3 signaling up-regulates epidermal growth factor receptor and enhances epidermal growth factor receptor-mediated carcinogenic activities in cultured lung adenocarcinoma cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Int J Oncol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3892/ijo.2012.1379"}], "href": "https://doi.org/10.3892/ijo.2012.1379"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22344462"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22344462"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "JinChao Hou, QiXing Chen, XiaoLiang Wu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "S1PR3 Signaling Drives Bacterial Killing and Is Required for Survival in Bacterial Sepsis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Am J Respir Crit Care Med (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1164/rccm.201701-0241OC"}], "href": "https://doi.org/10.1164/rccm.201701-0241OC"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28850247"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28850247"}]}, {"type": "r", "ref": 15, "children": [{"type": "t", "text": "Shushu Wang, Yueyang Liang, Wenxiao Chang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Triple Negative Breast Cancer Depends on Sphingosine Kinase 1 (SphK1)/Sphingosine-1-Phosphate (S1P)/Sphingosine 1-Phosphate Receptor 3 (S1PR3)/Notch Signaling for Metastasis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Med Sci Monit (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.12659/msm.905833"}], "href": "https://doi.org/10.12659/msm.905833"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "29605826"}], "href": "https://pubmed.ncbi.nlm.nih.gov/29605826"}]}, {"type": "r", "ref": 16, "children": [{"type": "t", "text": "Jiawei Zhao, Jingjing Liu, Jen-Fu Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TGF-β/SMAD3 Pathway Stimulates Sphingosine-1 Phosphate Receptor 3 Expression: IMPLICATION OF SPHINGOSINE-1 PHOSPHATE RECEPTOR 3 IN LUNG ADENOCARCINOMA PROGRESSION."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M116.740084"}], "href": "https://doi.org/10.1074/jbc.M116.740084"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27856637"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27856637"}]}, {"type": "r", "ref": 17, "children": [{"type": "t", "text": "Hui Min Lee, Kwok-Wai Lo, Wenbin Wei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Oncogenic S1P signalling in EBV-associated nasopharyngeal carcinoma activates AKT and promotes cell migration through S1P receptor 3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Pathol (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/path.4879"}], "href": "https://doi.org/10.1002/path.4879"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28240350"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28240350"}]}, {"type": "r", "ref": 18, "children": [{"type": "t", "text": "Lorenzo Magrassi, Nicola Marziliano, Frediano Inzani, et al. "}, {"type": "b", "children": [{"type": "t", "text": "EDG3 and SHC3 on chromosome 9q22 are co-amplified in human ependymomas."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cancer Lett (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.canlet.2009.08.023"}], "href": "https://doi.org/10.1016/j.canlet.2009.08.023"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19748727"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19748727"}]}, {"type": "r", "ref": 19, "children": [{"type": "t", "text": "Muhammad Yasir Asghar, Tero Viitanen, Kati Kemppainen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine 1-phosphate and human ether-a'-go-go-related gene potassium channels modulate migration in human anaplastic thyroid cancer cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Endocr Relat Cancer (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1530/ERC-12-0092"}], "href": "https://doi.org/10.1530/ERC-12-0092"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22889737"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22889737"}]}, {"type": "r", "ref": 20, "children": [{"type": "t", "text": "Changyong Li, Sujun Zheng, Hong You, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine 1-phosphate (S1P)/S1P receptors are involved in human liver fibrosis by action on hepatic myofibroblasts motility."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hepatol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jhep.2010.08.028"}], "href": "https://doi.org/10.1016/j.jhep.2010.08.028"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21145832"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21145832"}]}, {"type": "r", "ref": 21, "children": [{"type": "t", "text": "Le Yang, Shi Yue, Lin Yang, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine kinase/sphingosine 1-phosphate (S1P)/S1P receptor axis is involved in liver fibrosis-associated angiogenesis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Hepatol (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jhep.2013.02.021"}], "href": "https://doi.org/10.1016/j.jhep.2013.02.021"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23466305"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23466305"}]}, {"type": "r", "ref": 22, "children": [{"type": "t", "text": "Katrin Sobel, Katalin Menyhart, Nina Killer, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine 1-phosphate (S1P) receptor agonists mediate pro-fibrotic responses in normal human lung fibroblasts via S1P2 and S1P3 receptors and Smad-independent signaling."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.426726"}], "href": "https://doi.org/10.1074/jbc.M112.426726"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23589284"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23589284"}]}, {"type": "r", "ref": 23, "children": [{"type": "t", "text": "Xihong Liu, Shi Yue, Changyong Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Essential roles of sphingosine 1-phosphate receptor types 1 and 3 in human hepatic stellate cells motility and activation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.22572"}], "href": "https://doi.org/10.1002/jcp.22572"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21660960"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21660960"}]}, {"type": "r", "ref": 24, "children": [{"type": "t", "text": "María Camprubí-Robles, Norbert Mair, Manfred Andratsch, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Sphingosine-1-phosphate-induced nociceptor excitation and ongoing pain behavior in mice and humans is largely mediated by S1P3 receptor."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Neurosci (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1523/JNEUROSCI.4479-12.2013"}], "href": "https://doi.org/10.1523/JNEUROSCI.4479-12.2013"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23392686"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23392686"}]}, {"type": "r", "ref": 25, "children": [{"type": "t", "text": "Linjing Gong, Xu Wu, Xinyi Li, et al. "}, {"type": "b", "children": [{"type": "t", "text": "S1PR3 deficiency alleviates radiation-induced pulmonary fibrosis through the regulation of epithelial-mesenchymal transition by targeting miR-495-3p."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Physiol (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcp.29138"}], "href": "https://doi.org/10.1002/jcp.29138"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31489649"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31489649"}]}, {"type": "r", "ref": 26, "children": [{"type": "t", "text": "Wenliang Zhang, Jiawei Zhao, Jen-Fu Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ETS-1-mediated transcriptional up-regulation of CD44 is required for sphingosine-1-phosphate receptor subtype 3-stimulated chemotaxis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.495218"}], "href": "https://doi.org/10.1074/jbc.M113.495218"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24064218"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24064218"}]}, {"type": "r", "ref": 27, "children": [{"type": "t", "text": "Tamar Licht, Lilia Tsirulnikov, Hadas Reuveni, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Induction of pro-angiogenic signaling by a synthetic peptide derived from the second intracellular loop of S1P3 (EDG3)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Blood (2003)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1182/blood-2002-12-3634"}], "href": "https://doi.org/10.1182/blood-2002-12-3634"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "12763936"}], "href": "https://pubmed.ncbi.nlm.nih.gov/12763936"}]}, {"type": "r", "ref": 28, "children": [{"type": "t", "text": "M Tölle, L Klöckl, A Wiedon, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Regulation of endothelial nitric oxide synthase activation in endothelial cells by S1P1 and S1P3."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2016.06.009"}], "href": "https://doi.org/10.1016/j.bbrc.2016.06.009"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27282481"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27282481"}]}, {"type": "r", "ref": 29, "children": [{"type": "t", "text": "Ryo Terao, Megumi Honjo, Kiyohito Totsuka, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The role of sphingosine 1-phosphate receptors on retinal pigment epithelial cells barrier function and angiogenic effects."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Prostaglandins Other Lipid Mediat (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.prostaglandins.2019.106365"}], "href": "https://doi.org/10.1016/j.prostaglandins.2019.106365"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31415870"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31415870"}]}, {"type": "r", "ref": 30, "children": [{"type": "t", "text": "Xiuqin Ni, Yulia Epshtein, Weiguo Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Interaction of integrin β4 with S1P receptors in S1P- and HGF-induced endothelial barrier enhancement."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biochem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/jcb.24770"}], "href": "https://doi.org/10.1002/jcb.24770"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24851274"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24851274"}]}]}]}