ArticlePhysiological reports2013
Sphingosine-1-phosphate acts as a key molecule in the direct mediation of renal fibrosis.
Article in Physiological reports, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Effect of peritoneal dialysate on peritoneal fibrosis.BMC nephrology · 2026Article
- Sphingolipid signaling in kidney diseases.American journal of physiology. Renal physiology · 2025Review
- G protein-coupled receptor-mediated renal fibrosis: a key focus on kidney disease drug development.Frontiers in pharmacology · 2025Review
- The Sphingosine 1-Phosphate Axis: an Emerging Therapeutic Opportunity for Endometriosis.Reproductive sciences (Thousand Oaks, Calif.) · 2023Review
- Probiotic potential of Saccharomyces cerevisiae GILA with alleviating intestinal inflammation in a dextran sulfate sodium induced colitis mouse model.Scientific reports · 2023Article
- Loss of sphingosine kinase 2 protects against cisplatin-induced kidney injury.American journal of physiology. Renal physiology · 2022Article
- A Rheostat of Ceramide and Sphingosine-1-Phosphate as a Determinant of Oxidative Stress-Mediated Kidney Injury.International journal of molecular sciences · 2022Review
- Detrimental role of sphingosine kinase 1 in kidney damage in DOCA-salt hypertensive model: evidence from knockout mice.BMC nephrology · 2020Article
- Knockout of Sphingosine Kinase 1 Attenuates Renal Fibrosis in Unilateral Ureteral Obstruction Model.American journal of nephrology · 2019Article
- Sphingosine-1-phosphate pathway in renal fibrosis.American journal of physiology. Renal physiology · 2018Review
- Sphingolipids and Redox Signaling in Renal Regulation and Chronic Kidney Diseases.Antioxidants & redox signaling · 2018Article
- Therapeutic effects of sphingosine kinase inhibitor N,N-dimethylsphingosine (DMS) in experimental chronic Chagas disease cardiomyopathy.Scientific reports · 2017Article
- The role of sphingosine 1-phosphate receptor 2 in bile-acid-induced cholangiocyte proliferation and cholestasis-induced liver injury in mice.Hepatology (Baltimore, Md.) · 2017Article
- Sphingosine Kinase 2 Deficiency Attenuates Kidney FibrosisJournal of the American Society of Nephrology : JASN · 2017Article
- Analysis of sphingolipids in human corneal fibroblasts from normal and keratoconus patients.Journal of lipid research · 2017Article
- Urinary collagen degradation products as early markers of progressive renal fibrosis.Journal of translational medicine · 2017Article
- Article
- New insights into sodium transport regulation in the distal nephron: Role of G-protein coupled receptors.World journal of biological chemistry · 2016Review
- Targeting tubulointerstitial remodeling in proteinuric nephropathy in rats.Disease models & mechanisms · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The major sphingolipid metabolite, sphingosine-1-phosphate (S1P), has important biological functions. S1P serves as a ligand for a family of five G-protein-coupled receptors with distinct signaling pathways regulating important biological pathways. S1P induces renal fibrosis through an inflammatory pathway. However, its direct fibrosis-inducing effect on the kidney has not been shown. The role of S1P as a direct mediator of renal fibrosis was investigated in normal rat kidney interstitial fibroblast (NRK-49F) cells (in vitro) and kidneys of a unilateral ureteral obstruction (UUO) mouse model (in vivo). To clarify the role of S1P in renal fibrosis, we adopted nude UUO mice with immune response deficits. NRK-49F cells were stimulated with various concentrations of exogenous S1P and FTY720 (a S1P receptor agonist) or N,N-dimethylsphingosine (DMS; a sphingosine kinase inhibitor). C57BL6 and nude UUO mice were pretreated with FTY720, DMS, or saline. Expression levels of alpha-smooth muscle actin (a-SMA), E-cadherin, collagen type 1 (COL1), collagen type 4 (COL4), tissue inhibitor of matrix metalloproteinase-1 (TIMP1), and plasminogen activator inhibitor-1 (PAI1) were examined. S1P stimulated fibrosis in NRK-49F cells and UUO mice. Increased a-SMA, COL1, COL4, TIMP1, and PAI1 and decreased E-cadherin expression levels were observed in both the S1P-stimulated cells and UUO mice. Nude UUO mouse kidneys expressed fibrotic markers. Fibrotic changes were successfully induced in both UUO and nude UUO mice, evident through prominent fibronectin and COL1 staining. These S1P-induced fibrotic changes were suppressed by FTY720 and DMS both in vitro and in vivo. Thus, S1P essentially and directly mediates renal fibrosis.
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