Ask about this productRelated genes to: S1PR2 antibody
- Gene:
- S1PR2 NIH gene
- Name:
- sphingosine-1-phosphate receptor 2
- Previous symbol:
- EDG5, DFNB68
- Synonyms:
- Gpcr13, H218, AGR16
- Chromosome:
- 19p13.2
- Locus Type:
- gene with protein product
- Date approved:
- 1999-03-09
- Date modifiied:
- 2019-04-23
Related products to: S1PR2 antibody
Related articles to: S1PR2 antibody
- Gut microbiota-derived metabolites play a crucial role in the development of breast cancer by remodeling the tumor microenvironment and regulating key signaling pathways. The composition of the microbiota is susceptible to various environmental factors, particularly exposure to oral antibiotics. However, direct causal evidence linking oral antibiotic use to breast cancer progression remains elusive. Herein, we demonstrate that oral administration of broad-spectrum antibiotics promotes triple-negative breast cancer (TNBC) progression . Multi-omics analysis reveals that oral antibiotic treatment induces gut microbial dysbiosis and reprograms host bile acid metabolism, leading to a marked increase in taurocholic acid (TCA). We further show that microbiota-derived TCA enters the systemic circulation, accumulates in tumors, and functions as a key mediator of the gut-tumor axis. Mechanistically, TCA facilitates tumor progression by both activating the S1PR2/PI3K/AKT signaling pathway within tumor cells and suppressing CD8 T cell infiltration and cytotoxic function in the tumor microenvironment. In summary, this study, using a mouse model, establishes a link between oral antibiotic-induced dysbiosis and accelerated breast cancer progression and proposes that TCA and its associated pathways may serve as potential targets for future TNBC therapies. - Source: PubMed
Publication date: 2026/05/25
Wen YixuanYe PingtingShao LujingLi QiDong Chunyan - Sphingolipids regulate essential cellular processes, with sphingosine-1-phosphate (S1P) emerging as a critical modulator of proliferation, migration, and differentiation. While intracellular S1P governs sphingolipid metabolism during renal epithelial differentiation, its role as a ligand for S1P receptors (S1PRs) remains poorly understood. Here, we investigated the roles of S1PR1, S1PR2, and S1PR3 during the differentiation of Madin-Darby canine kidney (MDCK) cells. We found that S1PR2 and S1PR3 are critical for apical membrane formation, while S1PR2 additionally regulates adherens junction (AJ) maturation and actin cytoskeleton reorganization, essential for a differentiated epithelial morphology. Functional assays, including pharmacological inhibition and genetic silencing, showed that inhibition of S1PR2 impaired AJ formation and disrupted epithelial differentiation. Notably, S1PR2 restoration re-established AJ formation and epithelial organization, which underscores its critical role in maintaining cell-cell adhesion. Interestingly, S1PR2 exhibited distinct localization patterns throughout the differentiation process, transitioning from predominantly intracellular structures in proliferating cells to a more discrete peripheral/plasma membrane distribution along cell-cell boundaries in differentiated cells. These findings provide new insights into the spatial regulation of S1P signaling during renal epithelial differentiation and highlighted the emerging role of S1PR signaling in epithelial cell organization. This work broadens our understanding of S1PR2 mechanisms and suggests differential roles across stages of epithelial differentiation, thus offering potential therapeutic strategies for conditions involving renal epithelial dysfunction. - Source: PubMed
Publication date: 2026/05/08
Romero Daniela JudithPescio Lucila GiseleLoiacono GermánPalavecino Agustín NicolásFernández Federico EmanuelAlvarez Maria BelénSantacreu Bruno JaimeDel Valle Guaytima EdithFavale Nicolás Octavio - Traumatic brain injury (TBI) is a major cause of blood-brain barrier (BBB) disruption and neurological dysfunction, wherein endothelial dysfunction plays a critical pathogenic role. As a member of the G protein-coupled receptor family, sphingosine-1-phosphate receptor 2 (S1PR2) is known to regulate vascular homeostasis; however, its specific role in protecting the blood-brain barrier following TBI remains unclear. This study aims to elucidate the mechanism by which S1PR2 maintains blood-brain barrier integrity and to evaluate the therapeutic potential of S1PR2 inhibition after TBI. A mouse model of TBI was established using controlled cortical impact, while human umbilical vein endothelial cells (HUVECs) were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) to mimic ischemia-reperfusion injury in vitro. We employed shRNA technology to knock down S1PR2 expression and utilized single-cell RNA sequencing (dataset GSE269748) to characterize cell type-specific expression profiles. Endothelial function, blood-brain barrier permeability, inflammatory responses, and cell apoptosis were assessed using tube formation assays, transendothelial electrical resistance (TER) analysis, Western blotting, immunofluorescence, qPCR, ELISA, Evans blue staining, and brain water content measurements. Behavioral tests including open field test and novel object recognition test were used to evaluate the recovery of neurological function. At the same time, the PI3K-AKT pathway was interfered by S1PR2 knockdown mediated by AAV virus and pharmacological inhibitor (JTE-013/LY94002) or activator (Cyn). Single-cell analysis revealed that S1PR2 is specifically expressed in endothelial cells and is significantly upregulated following TBI. In vitro, S1PR2 knockdown counteracted the OGD/R-induced reduction in tube formation capacity and the elevation in transendothelial electrical resistance, and restored the expression of tight junction proteins Occludin and ZO-1. RNA-seq and KEGG enrichment analysis suggested that PI3K-AKT pathway was the key downstream target of S1PR2. In vivo experiments demonstrated that S1PR2 expression peaked at 72 h post-TBI and colocalized with CD31, while the ratios of p-PI3K/PI3K and p-AKT/AKT were markedly reduced. Intervention targeting S1PR2 significantly enhanced locomotor activity and novel object recognition, reduced brain lesion area, suppressed neuronal apoptosis and inflammatory cytokine levels, and restored BBB integrity in TBI mice. Mechanismally, activation of PI3K-AKT pathway could mimic the protective effect of S1PR2 knockdown, whereas inhibition of this pathway negated the improvements in BBB integrity and neurological function induced by S1PR2 knockdown. Endothelial S1PR2 is a critical regulator of vascular homeostasis after TBI. Inhibition of Endothelial S1PR2 preserves blood-brain barrier integrity, mitigates neuroinflammation and apoptosis, and promotes neurological recovery through activation of the PI3K-AKT signaling pathway, thereby offering a promising new strategy for targeted TBI therapy. - Source: PubMed
Publication date: 2026/05/08
Cheng HongboWang QinMen YijiaoAn YaqingMa BotaoDai ShimeiJing ZhuangHe XueruiBao XiaoqingLong YinboYu JiegangWu YangSun Guozhu - To investigate the effects of the sphingosine-1-phosphate receptor-2 (S1PR2) inhibitor JTE-013 on pulmonary fibrosis in silicosis mice and its underlying molecular mechanisms. In October 2024, 40 SPF male C57BL/6J mice were randomly divided into control group, JTE-013 control group, silicosis model group, and JTE-013 treatment group. A silicosis model was established by non-exposure intratracheal instillation of SiO(2) suspension. One week after model was establishment, mice in the JTE-013 treatment group were intraperitoneally injected with JTE-013 (10 mg/kg, twice a week for a total of 6 times), while mice in other groups were intraperitoneally injected with the same volume of normal saline. After 28 d of modeling, the lung coefficients of mice in each group were detected. The lung tissues were stained with HE, Masson, and Sirius Red to assess pathological damage and collagen deposition. The content of hydroxyproline (HYP) was determined. The expressions of S1PR2, epithelial-mesenchymal transition (EMT) marker proteins [E-cadherin (E-cad), Vimentin, α-smooth muscle actin (α-SMA) ], and Ras homolog family member A/Rho-related coiled helix kinase 1 (RhoA/ROCK1) pathway proteins were detected by protein immunoblotting method. Human alveolar epithelial A549 cells were cultured in vitro. The cells were divided into normal control group (cultured in complete medium for 26 h), JTE-013 control group (cultured in medium prepared to 1 μmol/L JTE-013 solution for 26 h), SiO(2) treatment group (cultured for 2 h with normal medium, then treated with 50 μg/ml SiO(2) suspension for 24 h), and SiO(2)+JTE-013 treatment group (pre-treated with 1 μmol/L JTE-013 for 2 h, then added 50 μg/ml SiO(2) suspension for 24 h). After group intervention, the expression levels of S1PR2, EMT-related proteins, RhoA and ROCK1 in the cells were detected. For the normally distributed measurement data, one-way ANOVA analysis of variance was used for inter-group comparison, and LSD- test was used for pairwise comparison. Compared with the control group, the mice in the silicosis model group had a significant decrease in body weight, and their lung coefficient and HYP content were significantly increased (<0.05), silicotic nodules formed in the lungs, accompanied by collagen deposition. And the expression levels of SIPR2 protein, EMT-related proteins Vimentin, α-SMA, and the RhoA and ROCK1 proteins in signaling pathway were significantly increased, while the expression level of the epithelial marker E-cad was significantly decreased (<0.05). Compared with the silicosis model group, the mice in the JTE-013 treatment group had a significantly increase in body weight, the lung coefficient and HYP content were significantly decreased (<0.05), the pulmonary fibrosis was significantly reduced. And the expression levels of SIPR2 protein, EMT-related proteins Vimentin, α-SMA, and the RhoA and ROCK1 proteins in the signaling pathway were significantly decreased, while the expression level of the epithelial marker E-cad was significantly increased (<0.05). In the in vitro experiments, compared with the normal control group, the expression levels of EMT-related proteins Vimentin, α-SMA and the proteins RhoA and ROCK1 in the signaling pathway in the SiO(2) treatment group were significantly increased, while the expression level of the epithelial marker E-cad was significantly decreased (<0.05). Compared with the SiO(2) group, the expression levels of EMT-related proteins Vimentin, α-SMA, and the proteins RhoA and ROCK1 in the signaling pathway in the SiO(2)+JTE-013 treatment group were significantly decreased, while the expression level of the epithelial marker E-cad was significantly increased (<0.05) . JTE-013 can alleviate the pulmonary fibrosis in silicosis mice, which may be related to the inhibition of the EMT process through the RhoA/ROCK1 signaling pathway. - Source: PubMed
Zhang JWu SChen Y HZou MLi Y - Vascular calcification and osteoporosis often co-occur during postmenopause, end-stage renal disease, advancing age, and diabetes, leading to increased mortality and significant challenges in therapy. FAM19A5 (family with sequence similarity 19 [chemokine (C-C motif)-like], member A5), as a novel protective adipokine, has been identified to suppress postinjury neointima formation. However, the involvement of adipose-derived FAM19A5 in vascular calcification and osteoporosis remains unclear. - Source: PubMed
Publication date: 2026/05/06
Dong ZhaoShiyu YangWang HuanZhang JiaziXie NanDai RongboZhang SitingCai ZeyuLi ZhiqingZhu ShirongWang JinweiZhou BiaoKang JihongYu FangMeng HuaFu YiZhang LuxiaZhang LuChunli SongKong Wei