ArticlePloS one2013
Inhibition of sphingosine kinase-2 in a murine model of lupus nephritis.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Therapeutic potential of the sphingosine kinase 2 inhibitor opaganib.Pharmaceutical science advances · 2026Review
- Opaganib Protects Against High-Fat Diet-Induced Hypercholesterolemia and Liver Steatosis in Mice.Diabetes, metabolic syndrome and obesity : targets and therapy · 2026Article
- Case Report: Fabry disease overlapping with systemic lupus erythematosus in a pediatric patient.Frontiers in immunology · 2025Article
- Opaganib Promotes Weight Loss and Suppresses High-Fat Diet-Induced Obesity and Glucose Intolerance.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025Article
- The contribution of the sphingosine 1-phosphate signaling pathway to chronic kidney diseases: recent findings and new perspectives.Pflugers Archiv : European journal of physiology · 2024Review
- Regulation of macrophage polarization by targeted metabolic reprogramming for the treatment of lupus nephritis.Molecular medicine (Cambridge, Mass.) · 2024Review
- The Sphingolipid-Modulating Drug Opaganib Protects against Radiation-Induced Lung Inflammation and Fibrosis: Potential Uses as a Medical Countermeasure and in Cancer Radiotherapy.International journal of molecular sciences · 2024Article
- Mysterious sphingolipids: metabolic interrelationships at the center of pathophysiology.Frontiers in physiology · 2023Review
- A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury.International journal of molecular sciences · 2022Review
- Sphk2 deletion is involved in structural abnormalities and Th17 response but does not aggravate colon inflammation induced by sub-chronic stress.Scientific reports · 2022Article
- Recent Progress in the Development of Opaganib for the Treatment of Covid-19.Drug design, development and therapy · 2022Review
- Sphingosine kinase 2 restricts T cell immunopathology but permits viral persistence.The Journal of clinical investigation · 2020Article
- Sphingolipids and Diagnosis, Prognosis, and Organ Damage in Systemic Lupus Erythematosus.Frontiers in immunology · 2020Review
- Examination of the role of sphingosine kinase 2 in a murine model of systemic lupus erythematosus.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Sphingosine 1-Phosphate Receptors and Metabolic Enzymes as Druggable Targets for Brain Diseases.Frontiers in pharmacology · 2019Review
- Sphingosine kinase 2 activates autophagy and protects neurons against ischemic injury through interaction with Bcl-2 via its putative BH3 domain.Cell death & disease · 2017Article
- Sphingosine-1-phosphate is involved in inflammatory reactions in patients with Graves' orbitopathy.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2017Article
- Sphingosine 1-phosphate signaling impacts lymphocyte migration, inflammation and infection.Pathogens and disease · 2016Review
- Accelerated vascular disease in systemic lupus erythematosus: role of macrophage.Clinical immunology (Orlando, Fla.) · 2015Review
- Structure-activity relationship studies and in vivo activity of guanidine-based sphingosine kinase inhibitors: discovery of SphK1- and SphK2-selective inhibitors.Journal of medicinal chemistry · 2015Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Sphingosine-1-phosphate (S1P), a potent bioactive lipid, is emerging as a central mediator in inflammation and immune responses. We have previously implicated S1P and its synthetic enzyme sphingosine kinase (SK) in inflammatory and autoimmune disorders, including inflammatory bowel disease and rheumatoid arthritis. Generation of S1P requires phosphorylation of sphingosine by SK, of which there are two isoforms. Numerous studies have implicated SK1 in immune cell trafficking, inflammation and autoimmune disorders. In this study, we set out to determine the role of SK and S1P in lupus nephritis (LN). To this end, we examined S1P and dihydro-S1P (dh-S1P) levels in serum and kidney tissues from a mouse model of LN. Interestingly dh-S1P was significantly elevated in serum and kidney tissue from LN mice, which is more readily phosphorylated by SK2. Therefore, we employed the use of the specific SK2 inhibitor, ABC294640 in our murine model of LN. Treatment with ABC294640 did not improve vascular or interstitial pathology associated with LN. However, mice treated with the SK2 inhibitor did demonstrate decreases in glomerular pathology and accumulation of B and T cells in the spleen these were not statistically different from lpr mice treated with vehicle. LN mice treated with ABC294640 did not have improved urine thromboxane levels or urine proteinuria measurements. Both S1P and dh-S1P levels in circulation were significantly reduced with ABC294640 treatment; however, dh-S1P was actually elevated in kidneys from LN mice treated with ABC294640. Together these data demonstrate a role for SKs in LN; however, they suggest that inhibition of SK1 or perhaps both SK isoforms would better prevent elevations in S1P and dh-S1P and potentially better protect against LN.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.