Sphingosine-1-Phosphate Receptor 1 Is Involved in Non-Obese Diabetic Mouse Thymocyte Migration Disorders

Lemos, Julia P.; Smaniotto, Salete; Messias, Carolina Valença; Moreira, Otacílio C.; Cotta-de-Almeida, Vinı́cius; Dardenne, Mireille; Savino, Wilson; Mendes-da-Cruz, Daniella Arêas

doi:10.3390/ijms19051446

Cited by 10 publications

(11 citation statements)

References 38 publications

(53 reference statements)

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“…The authors found that young female NOD mice who later progress to autoimmune diabetes exhibited the same lipidomic pattern as prediabetic children [164], confirming that the NOD mouse is a valuable model to study the role of SLs in T1DM development. Moreover, NOD thymocytes were found to be characterized by a lower level of S1PR1 and a decreased SPL mRNA and protein expression comparing with healthy mice [177]. These changes were suggested to participate in the T-cell migratory abnormalities observed in NOD mice during diabetes development [177].…”

Section: Animal Modelsmentioning

confidence: 96%

“…Moreover, NOD thymocytes were found to be characterized by a lower level of S1PR1 and a decreased SPL mRNA and protein expression comparing with healthy mice [177]. These changes were suggested to participate in the T-cell migratory abnormalities observed in NOD mice during diabetes development [177]. S1P was shown to reduce CD4+ T-cell activation in NOD mice and to prevent vascular complications [178].…”

Section: Animal Modelsmentioning

confidence: 99%

“…Administration of glycoSLs has been widely used to assess their effects on islet autoimmunity in NOD mice. For instance, ganglioside GM1 decreased the rate of islet infiltration, attenuated production of proinflammatory cytokines (IL-1β, TNFα and IFNγ) and increased the level of NGF in islets [177]. The protective effects of sulfatide against autoimmunity have been recognized already many years ago when Buschard and colleagues demonstrated that the treatment with sulfatide or its precursor GalCer prevents diabetes in NOD mice [179].…”

Section: Animal Modelsmentioning

confidence: 99%

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Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells

Gurgul-Convey¹

2020

Cells

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Type 1 diabetes (T1DM) is a chronic autoimmune disease, with a strong genetic background, leading to a gradual loss of pancreatic beta-cells, which secrete insulin and control glucose homeostasis. Patients with T1DM require life-long substitution with insulin and are at high risk for development of severe secondary complications. The incidence of T1DM has been continuously growing in the last decades, indicating an important contribution of environmental factors. Accumulating data indicates that sphingolipids may be crucially involved in T1DM development. The serum lipidome of T1DM patients is characterized by significantly altered sphingolipid composition compared to nondiabetic, healthy probands. Recently, several polymorphisms in the genes encoding the enzymatic machinery for sphingolipid production have been identified in T1DM individuals. Evidence gained from studies in rodent islets and beta-cells exposed to cytokines indicates dysregulation of the sphingolipid biosynthetic pathway and impaired function of several sphingolipids. Moreover, a number of glycosphingolipids have been suggested to act as beta-cell autoantigens. Studies in animal models of autoimmune diabetes, such as the Non Obese Diabetic (NOD) mouse and the LEW.1AR1-iddm (IDDM) rat, indicate a crucial role of sphingolipids in immune cell trafficking, islet infiltration and diabetes development. In this review, the up-to-date status on the findings about sphingolipids in T1DM will be provided, the under-investigated research areas will be identified and perspectives for future studies will be given.

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Section: Animal Modelsmentioning

confidence: 96%

Section: Animal Modelsmentioning

confidence: 99%

Section: Animal Modelsmentioning

confidence: 99%

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Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells

Gurgul-Convey¹

2020

Cells

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“…Hormonal imbalance in the thymus can be involved in the control of the physiology of the organ in NOD mice and humans, as the properly maturation of the cells, cell adhesion, migration, accumulation and egress, by the modulation of ECM molecules and integrins, chemokines and chemokine receptors, sphingosine-1-phosphate and sphingosine-1-phosphate receptor 1 ( 10 , 64 , 65 , 89 ). As an example, GH/IGF-1 axis can modulate the expression of cytokines, chemokines and ECM molecules and receptors in the thymus ( 61 ).…”

Section: Future Developments and Concluding Remarksmentioning

confidence: 99%

Abnormal T-Cell Development in the Thymus of Non-obese Diabetic Mice: Possible Relationship With the Pathogenesis of Type 1 Autoimmune Diabetes

et al. 2018

Self Cite

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Type 1 diabetes (T1D) is an autoimmune disease caused by the destruction of insulin-producing cells in the pancreas, by direct interactions with autoreactive pancreas infiltrating T lymphocytes (PILs). One of the most important animal models for this disease is the non-obese diabetic (NOD) mouse. Alterations in the NOD mouse thymus during the pathogenesis of the disease have been reported. From the initial migratory disturbances to the accumulation of mature thymocytes, including regulatory Foxp3+ T cells, important mechanisms seem to regulate the repertoire of T cells that leave the thymus to settle in peripheral lymphoid organs. A significant modulation of the expression of extracellular matrix and soluble chemoattractant molecules, in addition to integrins and chemokine receptors, may contribute to the progressive accumulation of mature thymocytes and consequent formation of giant perivascular spaces (PVS) that are observed in the NOD mouse thymus. Comparative large-scale transcriptional expression and network analyses involving mRNAs and miRNAs of thymocytes, peripheral T CD3+ cells and PILs provided evidence that in PILs chemokine receptors and mRNAs are post-transcriptionally regulated by miR-202-3p resulting in decreased activity of these molecules during the onset of T1D in NOD mice. In this review, we discuss the abnormal T-cell development in NOD mice in the context of intrathymic expression of different migration-related molecules, peptides belonging to the family of insulin and insulin-like growth factors as well as the participation of miRNAs as post-transcriptional regulators and their possible influence on the onset of aggressive autoimmunity during the pathogenesis of T1D.

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“…In spite of the relatively brief history of sphingosine-1-phosphate (S1P) as a biologically active lipid mediator, numerous reports highlight its major regulatory function in embryogenesis [1,2], the immune system and inflammation [3][4][5], the cardiovascular system [6][7][8][9][10], the nervous system [11][12][13], oncogenesis [14][15][16][17], as well as cellular motility and migration [18][19][20][21]. In the cardiovascular system, S1P has been implicated in the regulation of vasculo-and angiogenesis [22,23] and endothelial barrier function [24][25][26].…”

Section: Introductionmentioning

confidence: 99%

Sphingosine-1-Phosphate Enhances α1-Adrenergic Vasoconstriction via S1P2–G12/13–ROCK Mediated Signaling

Panta

Ruisanchez

Móré

et al. 2019

IJMS

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Sphingosine-1-phosphate (S1P) has been implicated recently in the physiology and pathology of the cardiovascular system including regulation of vascular tone. Pilot experiments showed that the vasoconstrictor effect of S1P was enhanced markedly in the presence of phenylephrine (PE). Based on this observation, we hypothesized that S1P might modulate α1-adrenergic vasoactivity. In murine aortas, a 20-minute exposure to S1P but not to its vehicle increased the Emax and decreased the EC50 of PE-induced contractions indicating a hyperreactivity to α1-adrenergic stimulation. The potentiating effect of S1P disappeared in S1P2 but not in S1P3 receptor-deficient vessels. In addition, smooth muscle specific conditional deletion of G12/13 proteins or pharmacological inhibition of the Rho-associated protein kinase (ROCK) by Y-27632 or fasudil abolished the effect of S1P on α1-adrenergic vasoconstriction. Unexpectedly, PE-induced contractions remained enhanced markedly as late as three hours after S1P-exposure in wild-type (WT) and S1P3 KO but not in S1P2 KO vessels. In conclusion, the S1P–S1P2–G12/13–ROCK signaling pathway appears to have a major influence on α1-adrenergic vasoactivity. This cooperativity might lead to sustained vasoconstriction when increased sympathetic tone is accompanied by increased S1P production as it occurs during acute coronary syndrome and stroke.

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Sphingosine-1-Phosphate Receptor 1 Is Involved in Non-Obese Diabetic Mouse Thymocyte Migration Disorders

Cited by 10 publications

References 38 publications

Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells

Sphingolipids in Type 1 Diabetes: Focus on Beta-Cells

Abnormal T-Cell Development in the Thymus of Non-obese Diabetic Mice: Possible Relationship With the Pathogenesis of Type 1 Autoimmune Diabetes

Sphingosine-1-Phosphate Enhances α1-Adrenergic Vasoconstriction via S1P2–G12/13–ROCK Mediated Signaling

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