ArticlePloS one2017
Unravelling the interplay of sphingolipids and TGF-β signaling in the human corneal stroma.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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Who cites it
17 citing papers in PubMed, 18 citations in OpenAlex.
- MEOX1 Coordinates Autocrine-Paracrine Programs via SPHK1/S1P to Promote Lymph Node Metastasis in Ovarian Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Sphingolipid Expression During Corneal Wound Healing in a Sphingosine Kinase 1 Knockout Model.Cells · 2026Article
- S1P, Generated by Sphingosine Kinase 1, Negatively Affects Corneal Wound Healing Process by Activating TGF-β/Smad Pathway.Analytical cellular pathology (Amsterdam) · 2026Article
- Metabolomic profiling in a rat model of visual fatigue associated with liver-kidney yin deficiency syndrome.Frontiers in endocrinology · 2025Article
- Amelioration of Fibrosis via S1P Inhibition Is Regulated by Inactivation of TGF-β and SPL Pathways in the Human Cornea.International journal of molecular sciences · 2024Article
- 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
- Potentiation of Sphingolipids and TGF-β in the human corneal stroma reveals intricate signaling pathway crosstalks.Experimental eye research · 2023Article
- The role of sphingosine-1-phosphate in the development and progression of Parkinson's disease.Frontiers in cellular neuroscience · 2023Review
- Ablation of Sphingosine Kinase 1 Protects Cornea from Neovascularization in a Mouse Corneal Injury Model.Cells · 2022Article
- Article
- FAK Inhibition Attenuates Corneal Fibroblast Differentiation In Vitro.Biomolecules · 2021Article
- Targeting the Sphingosine Kinase/Sphingosine-1-Phosphate Signaling Axis in Drug Discovery for Cancer Therapy.Cancers · 2021Review
- Inhibition of sphingosine kinase 2 attenuates hypertrophic scar formation via upregulation of Smad7 in human hypertrophic scar fibroblasts.Molecular medicine reports · 2020Article
- Modeling the cornea in 3-dimensions: Current and future perspectives.Experimental eye research · 2020Review
- Sphingosine Kinase 2 Phosphorylation of FTY720 is Unnecessary for Prevention of Light-Induced Retinal Damage.Scientific reports · 2019Article
- Inflammatory Ocular Diseases and Sphingolipid Signaling.Advances in experimental medicine and biology · 2019Review
- Sphingolipids as Emerging Mediators in Retina Degeneration.Frontiers in cellular neuroscience · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo delineate the role of Sphingolipids (SPLs) in the human cornea and their cross-talks with transforming growth factor beta (TGF-β) in order to develop novel, non-invasive therapies.
methodsHuman corneal fibroblasts (HCFs) were harvested from healthy donors, stimulated with Vitamin C to promote extracellular matrix assembly, treated with exogenous sphingosine-1-phosphate (S1P) or sphingosine kinase inhibitor 2 (SPHK I2) and isolated after 4 weeks for further analysis.
resultsData showed that S1P led to a significant decrease in cellular migration where SPHK I2 just delayed it for 24h. Significant modulation of the sphingolipid pathway was also noted. Sphingosine kinase-1 (SphK1) was significantly downregulated upon exogenous stimulation with S1P at a concentration of 5μM and Sphingosine kinase-2 (SphK2) was also significantly downregulated at concentrations of 0.01μM, 0.1μM, and 5μM; whereas no effects were observed upon stimulation with SPHK I2. S1PR3 was significantly downregulated by 0.1μM and 5μM S1P and upregulated by 5μM and 10μM SPHK I2. Furthermore, both S1P and SPHK I2 regulated corneal fibrosis markers such as alpha-smooth muscle actin, collagen I, III, and V. We also investigated the interplay between two TGF-β isoforms and S1P/SPHK I2 treatments and found that TGF-β1 and TGF-β3 were both significantly upregulated with the 0.1μM S1P but were significantly downregulated with the 5μM S1P concentration. When TGF-β1 was compared directly to TGF-β3 expression, we observed that TGF-β3 was significantly downregulated compared to TGF-β1 in the 5μM concentration of S1P. No changes were observed upon SPHK I2 treatment.
conclusionOur study delineates the role of sphingolipids in the human cornea and highlights their different activities based on the cell/tissue type.
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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.