ArticleScience translational medicine2022
Sphingosine 1-phosphate signaling in perivascular cells enhances inflammation and fibrosis in the kidney.
Article in Science translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 54 citations in OpenAlex.
- Microglia-independent rAAV-induced inflammation causes persistent ocular immune dysregulation rescued by S1P receptor modulation.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Mechanistic insights and therapeutic potential of sphingosine‑1‑phosphate in the development of pulmonary fibrosis (Review).Molecular medicine reports · 2026Review
- SPNS2 exports sphingosine-1-phosphate and imports glucose.Nature communications · 2026Article
- Mechanisms of IL-17A Neutralisation in Alleviating Renal Fibrosis and Inflammation in Spontaneously Hypertensive Rats.Clinical and experimental pharmacology & physiology · 2026Article
- Lipidomic Analysis of Plasma Extracellular Vesicles from Adiponectin Deficient Mice or Metabolic Syndrome Patients Reveals Pro-Oxidative and Pro-Inflammatory Lipid Signatures Correlating with Metabolic Dysfunction.Journal of extracellular vesicles · 2026Article
- Sphingolipid Metabolism in the Pathogenesis of Hashimoto's Thyroiditis.International journal of molecular sciences · 2025Review
- Renal tubular epithelial IGFBP7 interacts with PKM2 to drive renal lipid accumulation and fibrosis.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Pulsed ultrasound targeted to the spleen mitigates against kidney injury and promotes kidney repair.American journal of physiology. Renal physiology · 2025Article
- ALKBH5 regulates intrauterine adhesion progression through m6A dependent FABP4 mRNA stabilization and serum lipid metabolism.Communications biology · 2025Article
- Exercise improves depressive-like behavior in adolescent mice by regulating sphingosine and ceramide metabolism through microglial CerS1.Communications biology · 2025Article
- Sphingosine-1-Phosphate Receptor 2 Promotes Renal Microvascular Constriction and Kidney Injury Following Renal Ischemia-Reperfusion in Rats.Function (Oxford, England) · 2025Article
- Sphingosine kinase 1 inhibition aggravates vascular smooth muscle cell calcification.Pflugers Archiv : European journal of physiology · 2025Article
- Multiplatform Metabolomic Profiling of the Unilateral Ureteral Obstruction Murine Model of CKD.International journal of molecular sciences · 2025Article
- Assessment of Spinster homologue 2 (Spns2)-dependent transport of sphingosine-1-phosphate as a therapeutic target.British journal of pharmacology · 2025Article
- Sphingolipid signaling in kidney diseases.American journal of physiology. Renal physiology · 2025Review
- Gut microbial metabolite, sphingosine-1-phosphate (S1P), drives mesangial cell phenotypic transformation and accelerates progression of IgA nephropathy via CCL2-MET-FAK pathway.Current research in microbial sciences · 2025Article
- Identification of key lipid metabolism-related genes in kidney fibrosis: implications for chronic kidney disease management.Frontiers in physiology · 2025Article
- Metabolism at the crossroads of inflammation and fibrosis in chronic kidney disease.Nature reviews. Nephrology · 2025Review
- 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
- Sphingolipids and Chronic Kidney Disease.Journal of clinical medicine · 2024Review
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20 authors at 4 institutions in 2 countries.
Funding
Abstract
Chronic kidney disease (CKD), characterized by sustained inflammation and progressive fibrosis, is highly prevalent and can eventually progress to end-stage kidney disease. However, current treatments to slow CKD progression are limited. Sphingosine 1-phosphate (S1P), a product of sphingolipid catabolism, is a pleiotropic mediator involved in many cellular functions, and drugs targeting S1P signaling have previously been studied particularly for autoimmune diseases. The primary mechanism of most of these drugs is functional antagonism of S1P receptor-1 (S1P1) expressed on lymphocytes and the resultant immunosuppressive effect. Here, we documented the role of local S1P signaling in perivascular cells in the progression of kidney fibrosis using primary kidney perivascular cells and several conditional mouse models. S1P was predominantly produced by sphingosine kinase 2 in kidney perivascular cells and exported via spinster homolog 2 (Spns2). It bound to S1P1 expressed in perivascular cells to enhance production of proinflammatory cytokines/chemokines upon injury, leading to immune cell infiltration and subsequent fibrosis. A small-molecule Spns2 inhibitor blocked S1P transport, resulting in suppression of inflammatory signaling in human and mouse kidney perivascular cells in vitro and amelioration of kidney fibrosis in mice. Our study provides insight into the regulation of inflammation and fibrosis by S1P and demonstrates the potential of Spns2 inhibition as a treatment for CKD and potentially other inflammatory and fibrotic diseases that avoids the adverse events associated with systemic modulation of S1P receptors.
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