ArticlePloS one2018
Cell-intrinsic sphingosine kinase 2 promotes macrophage polarization and renal inflammation in response to unilateral ureteral obstruction.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- A Review of CXCL1 in Cardiac Fibrosis.Frontiers in cardiovascular medicine · 2021Pooled it
- Cisplatin-Induced Nephrotoxicity Attenuation byInternational journal of molecular sciences · 2026Article
- Therapeutic Regulation of Macrophage Polarization for Diabetic Kidney Disease by Targeted Metabolic Reprogramming.Current medical science · 2026Review
- Emerging therapeutic pipelines on kidney fibrosis: challenges in translational research.Journal of translational medicine · 2026Review
- Metformin Induces Changes in Sphingosine-1-Phosphate-Related Signaling in Diabetic Mice Brain.International journal of molecular sciences · 2025Article
- Identification of exosome miRNAs regulated by SPHK2 in human glioma cells.Frontiers in oncology · 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
- Deletion of Sphingosine Kinase 2 Attenuates Acute Kidney Injury in Mice with Hemolytic-Uremic Syndrome.International journal of molecular sciences · 2024Article
- Regulation of macrophage polarization by targeted metabolic reprogramming for the treatment of lupus nephritis.Molecular medicine (Cambridge, Mass.) · 2024Review
- Signaling controversy and future therapeutical perspectives of targeting sphingolipid network in cancer immune editing and resistance to tumor necrosis factor-α immunotherapy.Cell communication and signaling : CCS · 2024Review
- A comprehensive multiomics approach reveals that high levels of sphingolipids in cardiac cachexia adipose tissue are associated with inflammatory and fibrotic changes.Lipids in health and disease · 2023Article
- Nuclear SPHK2/S1P induces oxidative stress and NLRP3 inflammasome activation via promoting p53 acetylation in lipopolysaccharide-induced acute lung injury.Cell death discovery · 2023Article
- Hepatitis C Virus Infection Upregulates Plasma Phosphosphingolipids and Endocannabinoids and Downregulates Lysophosphoinositols.International journal of molecular sciences · 2023Article
- Targeting immunometabolism during cardiorenal injury: roles of conventional and alternative macrophage metabolic fuels.Frontiers in physiology · 2023Review
- The Impact of Sphingosine Kinases on Inflammation-Induced Cytokine Release and Vascular Endothelial Barrier Integrity.International journal of molecular sciences · 2022Article
- Loss of sphingosine kinase 2 protects against cisplatin-induced kidney injury.American journal of physiology. Renal physiology · 2022Article
- Sphk1 and Sphk2 Differentially Regulate Erythropoietin Synthesis in Mouse Renal Interstitial Fibroblast-like Cells.International journal of molecular sciences · 2022Article
- A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury.International journal of molecular sciences · 2022Review
- S1P Stimulates Erythropoietin Production in Mouse Renal Interstitial Fibroblasts by S1PInternational journal of molecular sciences · 2021Article
- Proteoglycan 4 (PRG4) expression and function in dry eye associated inflammation.Experimental eye research · 2021Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
Sphingosine Kinase-2 (Sphk2) is responsible for the production of the bioactive lipid Sphingosine-1 Phosphate, a key regulator of tissue repair. Here we address the in vivo significance of Sphingosine Kinase -2 in renal inflammation/fibrosis in response to unilateral ureteral obstruction using both genetic and pharmacological strategies. Obstructed kidneys of Sphk2-/- mice showed reduced renal damage and diminished levels of the renal injury markers TGFβ1 and αSMA when compared to wild type controls. We found a consistently significant increase in anti-inflammatory (M2) macrophages in obstructed Sphk2-/- kidneys by flow cytometry and a decrease in mRNA levels of the inflammatory cytokines, MCP1, TNFα, CXCL1 and ILβ1, suggesting an anti-inflammatory bias in the absence of Sphk2. Indeed, metabolic profiling showed that the pro-inflammatory glycolytic pathway is largely inactive in Sphk2-/- bone marrow-derived macrophages. Furthermore, treatment with the M2-promoting cytokines IL-4 or IL-13 demonstrated that macrophages lacking Sphk2 polarized more efficiently to the M2 phenotype than wild type cells. Bone marrow transplant studies indicated that expression of Sphk2-/- on either the hematopoietic or parenchymal cells did not fully rescue the pro-healing phenotype, confirming that both infiltrating M2-macrophages and the kidney microenvironment contribute to the damaging Sphk2 effects. Importantly, obstructed kidneys from mice treated with an Sphk2 inhibitor recapitulated findings in the genetic model. These results demonstrate that reducing Sphk2 activity by genetic or pharmacological manipulation markedly decreases inflammatory and fibrotic responses to obstruction, resulting in diminished renal injury and supporting Sphk2 as a novel driver of the pro-inflammatory macrophage phenotype.
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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.