Ask about this productRelated genes to: EDG8 antibody
- Gene:
- S1PR5 NIH gene
- Name:
- sphingosine-1-phosphate receptor 5
- Previous symbol:
- EDG8
- Synonyms:
- Edg-8
- Chromosome:
- 19p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 2001-01-02
- Date modifiied:
- 2014-11-19
Related products to: EDG8 antibody
Related articles to: EDG8 antibody
- Sphingosine-1-phosphate (S1P) is a crucial sphingolipid mediator in vasculature and neovascular eye diseases by controlling angiogenesis, inflammation and fibrosis. Five S1P receptors (S1PRs) are key therapeutic targets, with several S1PR-targeted drugs already in clinical use or trials. However, the vascular function of its major metabolic product, the reactive lipid aldehyde 2-hexadecenal (2-HD), remains unexplored. Here, we show that loss of the aldehyde dehydrogenase ALDH3B1 impairs 2-HD detoxification and leads to retinal vascular abnormalities in zebrafish, without affecting the trunk vasculature. Mechanistically, multi-omics analyses reveal that 2-HD accumulation disrupts iron homeostasis and induces ferroptosis by directly interacting with S1PR5. This finding is supported by integrative analyses of single-cell RNA sequencing and RNA sequencing from human neovascular retinal samples, identifying S1PR5 as a clinically relevant target. These findings uncover a previously unrecognized role of S1P derived 2-HD in vasculature and retinal vascular homeostasis, suggesting that targeting S1PR5 could offer a therapeutic strategy for diabetic retinopathy. - Source: PubMed
Publication date: 2026/04/14
Qian XinGe RuiChu YintengKuang TianZhang XinBennewitz KatrinLou BowenHao WeijieAst VolkerKlinke GlynisPoschet GernotMorgenstern JakobFleming ThomasHausser IngridSzendroedi JuliaNawroth Peter PaulKroll Jens - Sphingosine-1-phosphate (S1P), a key metabolite of sphingolipids, plays crucial roles in a wide range of physiological and pathological processes. S1P primarily exerts its functions by binding to G protein-coupled sphingosine-1-phosphate receptors (S1PRs), which comprise five subtypes (S1PR1-5) in humans, thereby activating these receptors and their downstream signaling pathways. Understanding the molecular determinants that govern agonist selectivity among different S1PR subtypes is vital for the rational and precise development of targeted therapeutic agents. Here, four cryo-electron microscopy structures of agonist-bound S1PR1-Gi1 complexes are reported. Through an integrated approach combining structural analysis, molecular dynamics simulations, and pharmacological assays, the molecular basis for the selectivity of CYM5442, HY-X-1011, Ponesimod, and SAR247799 toward S1PR1 over S1PR2-S1PR5 is uncovered. Nonconserved residues within the ligand-binding pocket and at the Gi1-protein interface contribute to S1PR1 selectivity by these agonists. A distinct agonist binding orientation toward transmembrane helices 5-7, combined with branched substituents that increase the agonist's molecular width, results in steric clashes with residues in S1PR3. Additionally, branched moieties located at the tail portions of the agonist restrict its deep insertion into the binding pocket of both S1PR3 and S1PR5. These structural features collectively enhance its selectivity for S1PR1 over S1PR3 and S1PR5. Furthermore, polar interactions with conserved polar residues in the top region of the binding pocket also influence agonist selectivity. Besides, the relatively broad molecular width of the agonist sterically hinders its binding into S1PR2 and S1PR4 pocket by nonconserved residue pairs bearing bulky side chains. These findings establish a structural framework for the rational design of next-generation S1PR1 highly selective agonists with improved therapeutic potential. - Source: PubMed
Publication date: 2026/04/10
Yu LeiyeJiao HaizhanPang BinTi RujuanGan BingQin ZhaoyangWang JinxinZhu LizheHu HongliRen Ruobing - Atopic dermatitis (AD) is a common inflammatory skin disease associated with Th2, Th9, and Th22 skewing. Recent studies have implicated various lipid mediators in modulating T helper cell responses. However, the relationship between lipid mediators and Th skewing in AD is not fully understood. - Source: PubMed
Publication date: 2026/03/17
Yamamura KazuhikoGarcet SandraGonzalez JuanaZhou JerryFiedler JacobMiura ShunsukeWilliams Samuel CHur Hong BeomMurai-Yamamura MikaLi XuanRenert-Yuval YaelEstrada YerielKrueger James GGuttman-Yassky Emma - Tissue-resident lymphocytes can recirculate, but the underlying molecular mechanism is poorly understood. During helminth infection, intestinal group 2 innate lymphoid cells (ILC2s) rapidly proliferate and give rise to inflammatory ILC2s (iILC2s), which migrate from the intestine to distal tissues. Here, we show in mice that the redistribution of iILC2s requires access to lymphatic vessels. Interleukin-25 (IL-25) induces a substantial change in the epigenetic landscape of iILC2s, with transcription factors KLF2 and ZEB2 driving increased expression of sphingosine-1-phosphate receptor 1 (S1PR1) and S1PR5, respectively. S1PR5 regulates iILC2 exit from the intestine to the lymph, whereas S1PR1 is critical for iILC2 egress from the mesenteric lymph nodes to the blood and then to distal tissues including the lung, where iILC2s contribute to tissue repair. The requirement of two S1PRs is largely due to the dynamic expression of CD69, which mediates S1PR1 internalization. Thus, S1PRs modulate iILC2 emigration from nonlymphoid and lymphoid organs in a stage-specific manner, which provides a framework for understanding the multistep migration of tissue-resident immune cells. - Source: PubMed
Publication date: 2026/03/13
Ito TakamasaWu Christine FZhang YingyuIshida YoshihiroGretarsson Kristjan HXu XinjingZou RaymondGuichard VincentHuang Lei HHan Richard PGuckian KevinChun JeroldQue JianwenSmith AllenUrban Joseph FLu ChaoHuang Yuefeng - Sphingosine-1-phosphate (S1P) receptor agonists have emerged as promising therapeutics for autoimmune diseases, due to their crucial roles in regulating lymphocyte migration, differentiation, and cytokine secretion. Here, a series of novel 3-(naphthalene-1-yl)-1,2,4-oxadiazol derivatives are designed and synthesized as orally bioavailable, selective dual agonists of S1PR1 and S1PR5. Compounds and were identified, exhibiting excellent in vitro agonistic activity and more than 1000-fold selectivity over S1PR2, S1PR3, and S1PR4. Neither compound and displayed detectable agonistic activity toward S1PR3, they demonstrated favorable pharmacokinetic properties and, in contrast to FTY720, showed minimal impact on heart rate in mice. In a dextran sodium sulfate-induced mouse model of inflammatory bowel disease (IBD), compounds and significantly alleviated colitis pathology. Their mechanism of action was further confirmed through S1PR1-dependent inhibition of T cell migration. Collectively, these findings identify compounds and as promising lead candidates for the treatment of IBD. - Source: PubMed
Publication date: 2026/02/19
Wei XinxinYuan KaixiongZhao JingjieGao FengLi JingWang YongHu ShuleiXie CenLiu YamengLiu HongWang Jiang