Sphk1/S1P/S1PR1 Signaling is Involved in the Development of Autoimmune Thyroiditis in Patients and NOD.H-2<sup>h4</sup> Mice

Han, Cheng; He, Xue; Xia, Xin; Guo, Jiahui; Liu, Aihua; Liu, Xin; Wang, Xinyi; Li, Chengyan; Peng, Siyun; Zhao, Wei; Zhou, Mei; Shi, Xiaoguang; Li, Yushu; Li, Yongze; Shan, Zhongyan; Wang, Teng

doi:10.1089/thy.2018.0065

Cited by 13 publications

(16 citation statements)

References 48 publications

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“…found that Sphk1/S1P/S1PR1 signal transduction is involved in the development of mice autoimmune thyroiditis (AIT). In AIT mice, the proportions of inflammation-related cell subtypes (such as Th1, Th17 and Tfh) are elevated, while FTY720 administration can decrease the their levels, suggesting that suppression of Sphk1/S1P/S1PR1 signaling pathway may be a potential therapeutic target of AIT ( 31 ). In this study, we found that sphinganine decreased, while S1P levels increased in the GD group.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive Metabolomics Study in Children With Graves’ Disease

et al. 2021

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ObjectiveGraves’ disease (GD) related hyperthyroidism (HT) has profound effects on metabolic activity and metabolism of macromolecules affecting energy homeostasis. In this study, we aimed to get a comprehensive understanding of the metabolic changes and their clinical relevance in GD children.MethodsWe investigated serum substances from 30 newly diagnosed GD children and 30 age- and gender-matched healthy controls. We explored the metabolomics using ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC-QTOF/MS) analysis, and then analyzed the metabolomic data via multivariate statistical analysis.ResultsBy untargeted metabolomic analysis, a total of 730 metabolites were identified in all participants, among which 48 differential metabolites between GD and control groups were filtered out, including amino acids, dipeptides, lipids, purines, etc. Among these metabolites, 33 were detected with higher levels, while 15 with lower levels in GD group compared to controls. Pathway analysis showed that HT had a significant impact on aminoacyl-transfer ribonucleic acid (tRNA) biosynthesis, several amino acids metabolism, purine metabolism, and pyrimidine metabolism.ConclusionIn this study, via untargeted metabolomics analysis, significant variations of serum metabolomic patterns were detected in GD children.

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Section: Discussionmentioning

confidence: 99%

Comprehensive Metabolomics Study in Children With Graves’ Disease

et al. 2021

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“…Other conditions denoted by aberrant inflammatory immune cell activation with a potential to cause immune encephalitis have been reported recently. For example, in autoimmune thyroiditis an enhanced expression of SphK1, S1P, and S1P 1 converging on STAT3 activation in CD4 + T cells was demonstrated in mice by Han et al [201]. Conversely, administration of fingolimod to these NOD.H-2 h4 mice conferred the potential to reduce disease severity accompanied by a reduction of STAT3-related cell types, i.e., T H 1, T H 17, and T FH cells [201].…”

Section: The Sphingolipid Metabolism In Neuroinflammatory Disordersmentioning

confidence: 99%

The S1P–S1PR Axis in Neurological Disorders—Insights into Current and Future Therapeutic Perspectives

Lucaciu

Brunkhorst

Pfeilschifter

et al. 2020

Cells

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Sphingosine 1-phosphate (S1P), derived from membrane sphingolipids, is a pleiotropic bioactive lipid mediator capable of evoking complex immune phenomena. Studies have highlighted its importance regarding intracellular signaling cascades as well as membrane-bound S1P receptor (S1PR) engagement in various clinical conditions. In neurological disorders, the S1P–S1PR axis is acknowledged in neurodegenerative, neuroinflammatory, and cerebrovascular disorders. Modulators of S1P signaling have enabled an immense insight into fundamental pathological pathways, which were pivotal in identifying and improving the treatment of human diseases. However, its intricate molecular signaling pathways initiated upon receptor ligation are still poorly elucidated. In this review, the authors highlight the current evidence for S1P signaling in neurodegenerative and neuroinflammatory disorders as well as stroke and present an array of drugs targeting the S1P signaling pathway, which are being tested in clinical trials. Further insights on how the S1P–S1PR axis orchestrates disease initiation, progression, and recovery may hold a remarkable potential regarding therapeutic options in these neurological disorders.

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“…Sphingolipids and their metabolic enzymes are key mediators in organisms. SphK1 and S1P play important roles in signal transduction and autoimmune diseases (Han et al, 2019). S1P is a sphingolipid metabolite with multiple biological activities that are widely distributed in various cell types.…”

Section: Discussionmentioning

confidence: 99%

Geniposide downregulates the VEGF/SphK1/S1P pathway and alleviates angiogenesis in rheumatoid arthritis in vivo and in vitro

Wang

Hong

Deng

et al. 2021

Phytotherapy Research

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The VEGF/SphK1/S1P pathway is closely related to angiogenesis in rheumatoid arthritis (RA), but the precise underlying mechanisms are unclear at present. Here, we explored the involvement of the VEGF/SphK1/S1P cascade in RA models and determined the effects of GE intervention. Our results showed abnormal expression of proteins related to this pathway in RA synovial tissue. Treatment with GE effectively regulated the signal axis, inhibited angiogenesis, and alleviated RA symptoms. In vitro, TNF‐ɑ enhanced the VEGF/SphK1/S1P pathway in a co‐culture model of fibroblast‐like synoviocytes (FLS) and vascular endothelial cells (VEC). GE induced downregulation of VEGF in FLS, restored the dynamic balance of pro‐/antiangiogenic factors, and suppressed SphK1/S1P signaling in VEC, resulting in lower proliferation activity, migration ability, tube formation ability, and S1P secretion ability of VEC cells. Additionally, SphK1‐specific small interfering RNA (siRNA) blocked the VEGF/SphK1/S1P cascade, which can effectively alleviate the stimulatory effect of FLS on VEC and further enhanced the therapeutic effect of GE. Taken together, our results demonstrate that GE suppresses the VEGF/SphK1/S1P pathway and alleviates the stimulation of VEC by FLS, thereby preventing angiogenesis and promoting therapeutic effects against RA.

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Sphk1/S1P/S1PR1 Signaling is Involved in the Development of Autoimmune Thyroiditis in Patients and NOD.H-2^h4 Mice

Cited by 13 publications

References 48 publications

Comprehensive Metabolomics Study in Children With Graves’ Disease

Comprehensive Metabolomics Study in Children With Graves’ Disease

The S1P–S1PR Axis in Neurological Disorders—Insights into Current and Future Therapeutic Perspectives

Geniposide downregulates the VEGF/SphK1/S1P pathway and alleviates angiogenesis in rheumatoid arthritis in vivo and in vitro

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Sphk1/S1P/S1PR1 Signaling is Involved in the Development of Autoimmune Thyroiditis in Patients and NOD.H-2h4 Mice

Cited by 13 publications

References 48 publications

Comprehensive Metabolomics Study in Children With Graves’ Disease

Comprehensive Metabolomics Study in Children With Graves’ Disease

The S1P–S1PR Axis in Neurological Disorders—Insights into Current and Future Therapeutic Perspectives

Geniposide downregulates the VEGF/SphK1/S1P pathway and alleviates angiogenesis in rheumatoid arthritis in vivo and in vitro

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Sphk1/S1P/S1PR1 Signaling is Involved in the Development of Autoimmune Thyroiditis in Patients and NOD.H-2^h4 Mice