Recent advances of the function of sphingosine 1‐phosphate (S1P) receptor S1P3

Fan, Xuehui; Liu, Huan; Shi, Yawei; Guo, Fanghan; Xiao, He; Zhao, Xueping; Zhong, Di; Li, Guozhong

doi:10.1002/jcp.29958

Cited by 16 publications

(9 citation statements)

References 110 publications

(159 reference statements)

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“…S1PR3, a member of the S1P receptor family, plays an essential role in the relevant pathophysiological processes of inflammation, cell proliferation, cell migration, cancer cell invasion and metastasis, I/R, tissue fibrosis, and vascular tone ( Fan et al, 2021 ). Previous studies show that astrocytic S1PR3 is upregulated during the neuroinflammatory response in highly permeable lesions and expressed in patients’ brain metastases.…”

Section: Discussionmentioning

confidence: 99%

S1PR3, as a Core Protein Related to Ischemic Stroke, is Involved in the Regulation of Blood–Brain Barrier Damage

Fan

Chen

et al. 2022

Front. Pharmacol.

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Background: Ischemic stroke is the most common stroke incident. Sphingosine-1-phosphate (S1P) receptor 3 (S1PR3) is a member of the downstream G protein-coupled receptor family of S1P. The effect of S1PR3 on ischemic stroke remains elusive.Methods: We downloaded two middle cerebral artery occlusion (MCAO) microarray datasets from the Gene Expression Omnibus (GEO) database and screened differentially expressed genes (DEGs). Then, we performed a weighted gene coexpression network analysis (WGCNA) and identified the core module genes related to ischemic stroke. We constructed a protein–protein interaction (PPI) network for the core genes in which DEGs and WGCNA intersected. Finally, we discovered that S1PR3 was involved as the main member of the red proteome. Then, we explored the mechanism of S1PR3 in the mouse tMCAO model. The S1PR3-specific inhibitor CAY10444 was injected into the abdominal cavity of mice after cerebral ischemia/reperfusion (I/R) injury, and changes in the expression of blood–brain barrier-related molecules were measured using PCR, western blotting, and immunofluorescence staining.Results: Both GEO datasets showed that S1PR3 was upregulated during cerebral I/R in mice. WGCNA revealed that the light yellow module had the strongest correlation with the occurrence of IS. We determined the overlap with DEGs, identified 146 core genes that are potentially related to IS, and constructed a PPI network. Finally, S1PR3 was found to be the main member of the red proteome. In the mouse cerebral I/R model, S1PR3 expression increased 24 h after ischemia. After the administration of CAY10444, brain edema and neurological deficits in mice were ameliorated. CAY10444 rescued the decreased expression of the tight junction (TJ) proteins zonula occludens 1 (ZO1) and occludin after ischemia induced by transient MCAO (tMCAO) and reduced the increase in aquaporin 4 (AQP4) levels after tMCAO, preserving the integrity of the BBB. Finally, we found that S1PR3 is involved in regulating the mitogen-activated protein kinase (MAPK) and (phosphatidylinositol-3 kinase/serine-threonine kinase) PI3K-Akt signaling pathways.Conclusion: S1PR3 participates in the regulation of blood–brain barrier damage after cerebral I/R. S1PR3 is expected to be an indicator and predictor of cerebral ischemia, and drugs targeting S1PR3 may also provide new ideas for clinical medications.

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Section: Discussionmentioning

confidence: 99%

S1PR3, as a Core Protein Related to Ischemic Stroke, is Involved in the Regulation of Blood–Brain Barrier Damage

Fan

Chen

et al. 2022

Front. Pharmacol.

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“…S1PR3 can be coupled to Gi/o, Gq, G12/13 families, causing activation of small GTPases such as Rho, Rac and Ras7. In addition, S1PR3 is widely expressed in humans, with high expression in the central nervous system (CNS), immune system, and cardiovascular system [7].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Influence of S1PR3 expression on the glioma microenvironment and prognostic significance in low-grade gliomas

Chen

Zhong

Xie

et al. 2022

Preprint

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Background The S1P/S1PR3 axis has been demonstrated to be associated with the development of multiple human cancers, but the potential role of it in the biological mechanisms of glioma, par-ticularly TME cell infiltration, remains unknown. Methods We analyzed gene expression data of gliomas and corresponding clinicopathological information to assess overall survival by univariate and multivariate Cox regression. We also analyzed the signaling pathways and genes associated with S1PR3 overexpression by Gene Set Enrichment Analysis, and the characteristics of oncogenic pathways, biological pathways, and TME cell infiltration, and validated the results with PCR, cell proliferation, and migration assays. Results Cox regression analysis confirmed that S1PR3 overexpression was significantly correlated with overall survival and clinicopathological features. Nomogram for prognostic prediction was successfully constructed using S1PR3 and related genes, and Gene Set Enrichment Analysis revealed the association of S1PR3 overexpression with cell cycle, DNA replication, MAPK, p53 and TGF-β signaling pathway. Meanwhile, S1PR3 was shown to be significantly associated with many immune checkpoints and immune cell infiltration. Conclusions Our study demon-strated that S1PR3 overexpression is a potential prognostic molecular marker for poor prognosis in glioma, that S1PR3 plays an important role in immune cell infiltration in TME. And identification of S1PR3-regulated signaling pathways and immune checkpoints enhances our understanding of TME infiltration characteristics, contributes to the development of immunotherapeutic strategies.

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“…S1P3 has the ability to couple to the Gi/o, Gq, and G12/13 families, activating small GTPases like Rho, Rac, and Ras7. S1P3 is also highly expressed in the central nervous system (CNS), immunological system, and cardiovascular system in humans (7).…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: S1P3 promotes low-grade glioma progression and affects tumor microenvironment infiltration

Huang

Wang

et al. 2022

Preprint

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Numerous human tumors have been demonstrated to develop in a manner that is correlated with the S1P/S1P3 axis. However, it is yet unclear how this axis could affect the development of glioma, specifically TME cell invasion. We examined the clinicopathological data and gene expression data of gliomas to evaluate overall survival using univariate and multivariate Cox regression. By using Gene Set Enrichment Analysis, we investigated the signaling pathways and genes linked to S1P3 overexpression. We also examined the traits of biological pathways, TME immune cell infiltration, and oncogenic pathways (OP) in glioma samples with different S1P3 expression levels, and we validated the findings using PCR, CCK8, and wound healing assays. S1P3 overexpression was substantially linked with molecular typing and overall survival, according to Cox regression analysis. The Nomogram for predicting prognosis was successfully constructed by using S1P3 and other molecular signatures of gliomas, and Gene Set Enrichment Analysis revealed the relationship between S1P3 overexpression and DNA replication, cell cycle, MAPK, p53 and TGF-β signaling pathways. In addition, S1P3 was significantly correlated with many immune checkpoints and immune cell infiltration. Overall, S1P3 overexpression is a potential prognostic molecular marker for poor prognosis in glioma. Additionally, S1P3 acts as an important player in TME immune cell infiltration. The identification of S1P3-regulated signaling pathways and immune checkpoints strengthens our understanding of TME infiltration signatures and contributes to the development of immunotherapeutic strategies.

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Recent advances of the function of sphingosine 1‐phosphate (S1P) receptor S1P3

Cited by 16 publications

References 110 publications

S1PR3, as a Core Protein Related to Ischemic Stroke, is Involved in the Regulation of Blood–Brain Barrier Damage

S1PR3, as a Core Protein Related to Ischemic Stroke, is Involved in the Regulation of Blood–Brain Barrier Damage

RETRACTED: Influence of S1PR3 expression on the glioma microenvironment and prognostic significance in low-grade gliomas

RETRACTED: S1P3 promotes low-grade glioma progression and affects tumor microenvironment infiltration

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