ArticleArthritis and rheumatism2010
Dihydrosphingosine 1-phosphate has a potent antifibrotic effect in scleroderma fibroblasts via normalization of phosphatase and tensin homolog levels.
Article in Arthritis and rheumatism, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 59 citations in OpenAlex.
- Trial
- Ceramides in Autoimmune Rheumatic Diseases: Existing Evidence and Therapeutic Considerations for Diet as an Anticeramide Treatment.Nutrients · 2023Review
- Analysis of the Sphingolipidome in NAFLD.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Dihydrosphingosine driven enrichment of sphingolipids attenuates TGFβ induced collagen synthesis in cardiac fibroblasts.International journal of cardiology. Heart & vasculature · 2021Article
- Lipid Alterations in Systemic Sclerosis.Frontiers in molecular biosciences · 2021Review
- Understanding Fibrosis in Systemic Sclerosis: Novel and Emerging Treatment Approaches.Current rheumatology reports · 2020Review
- Neonatal therapy with PF543, a sphingosine kinase 1 inhibitor, ameliorates hyperoxia-induced airway remodeling in a murine model of bronchopulmonary dysplasia.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Lipid Mediators Regulate Pulmonary Fibrosis: Potential Mechanisms and Signaling Pathways.International journal of molecular sciences · 2020Review
- Metabolic Targets for Treatment of Autoimmune Diseases.Immunometabolism · 2020Article
- The role of dihydrosphingolipids in disease.Cellular and molecular life sciences : CMLS · 2019Review
- Attenuation of murine sclerodermatous models by the selective S1PScientific reports · 2019Article
- Regulatory role of sphingosine kinase and sphingosine-1-phosphate receptor signaling in progenitor/stem cells.World journal of stem cells · 2018Review
- Sphingosine kinase 1 promotes liver fibrosis by preventing miR-19b-3p-mediated inhibition of CCR2.Hepatology (Baltimore, Md.) · 2018Article
- The Role of S1P and the Related Signaling Pathway in the Development of Tissue Fibrosis.Frontiers in pharmacology · 2018Review
- Interactions between TGF-β1, canonical WNT/β-catenin pathway and PPAR γ in radiation-induced fibrosis.Oncotarget · 2017Review
- PTP4A1 promotes TGFβ signaling and fibrosis in systemic sclerosis.Nature communications · 2017Article
- A modified graft-versus-host-induced model for systemic sclerosis, with pulmonary fibrosis in Rag2-deficient mice.FEBS open bio · 2017Article
- Protein Tyrosine Phosphatases in Systemic Sclerosis: Potential Pathogenic Players and Therapeutic Targets.Current rheumatology reports · 2017Review
- Article
- Description of the sphingolipid content and subspecies in the diabetic cornea.Current eye research · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectivePrevious studies have revealed a phosphatase and tensin homolog (PTEN)-dependent interaction between the sphingolipid agonist dihydrosphingosine 1-phosphate (dhS1P) and the transforming growth factor beta/Smad3 signaling pathway. This study was undertaken to examine responses of systemic sclerosis (SSc) fibroblasts to sphingosine 1-phosphate (S1P) and dhS1P and to gain further insight into the regulation of the S1P/dhS1P/PTEN pathway in SSc fibrosis.
methodsFibroblast cultures were established from skin biopsy samples obtained from patients with SSc and matched healthy controls. Western blotting and quantitative polymerase chain reaction were used to measure protein and messenger RNA levels, respectively. PTEN protein was examined in skin biopsy samples by immunohistochemistry.
resultsPTEN protein levels were low in SSc fibroblasts and correlated with elevated levels of collagen and phospho-Smad3 and reduced levels of matrix metalloproteinase 1 (MMP-1). Treatment with dhS1P restored PTEN levels and normalized collagen and MMP-1 expression, as well as Smad3 phosphorylation status in SSc fibroblasts. S1P was strongly profibrotic in SSc and control fibroblasts. Distribution of S1P receptor isoforms was altered in SSc fibroblasts, which had reduced levels of S1P receptor 1 and S1P receptor 2 and elevated levels of S1P receptor 3. Only depletion of S1P receptor 1 abrogated the effects of dhS1P and S1P in control dermal fibroblasts. In contrast, depletion of either S1P receptor 1 or S1P receptor 2 prevented the effects of S1P and dhS1P in SSc fibroblasts.
conclusionOur findings demonstrate that PTEN deficiency is a critical determinant of the profibrotic phenotype of SSc fibroblasts. The antifibrotic effect of dhS1P is mediated through normalization of PTEN expression, suggesting that dhS1P or its derivatives may be effective as therapeutic antifibrotic agents. The distribution and function of S1P receptors differ in SSc and healthy fibroblasts, suggesting that alteration in the sphingolipid signaling pathway may contribute to SSc fibrosis.
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