ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016
Sphingosine-1-phosphate phosphatase 2 promotes disruption of mucosal integrity, and contributes to ulcerative colitis in mice and humans.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 60 citations in OpenAlex.
- Plasma Levels of the Bioactive Sphingolipid Metabolite S1P in Adult Cystic Fibrosis Patients: Potential Target for Immunonutrition?Nutrients · 2020Trial
- Tissue and cellular spatiotemporal dynamics in colon aging.Nature biotechnology · 2026Article
- DKC1 promotes colorectal cancer progression and therapy resistance by dysregulating sphingolipid biosynthesis.Nature communications · 2026Article
- TFAP2A regulates SGPP2 transcription to promote lipid accumulation and activate the Wnt/β-catenin signaling pathway to promote malignant progression in lung adenocarcinoma.Journal of translational medicine · 2026Article
- CEBPD-mediated SGPP2 upregulation via PERK/ER stress in endothelial cells disrupts S1P homeostasis and impairs angiogenesis in chronic endometritis.Journal of translational medicine · 2025Article
- Mild features of partialFrontiers in pediatrics · 2025Article
- Sphingosine-1-phosphate alleviates colitis by regulating macrophage polarization and PI3k-Akt signaling.Frontiers in immunology · 2025Article
- The diverse roles of sphingolipids in inflammatory bowel disease.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- Comprehensive Analysis of Sphingolipid Metabolism-Related Genes in Osteoarthritic Diagnosis and Synovial Immune Dysregulation.Medical science monitor : international medical journal of experimental and clinical research · 2024Article
- Targeting Sphingosine-1-Phosphate Signaling in Breast Cancer.International journal of molecular sciences · 2024Review
- Therapeutic Potential for Sphingolipids in Inflammatory Bowel Disease and Colorectal Cancer.Cancers · 2024Review
- Review
- The role of ACER2 in intestinal sphingolipid metabolism and gastrointestinal cancers.Frontiers in immunology · 2024Review
- Immune System and Brain/Intestinal Barrier Functions in Psychiatric Diseases: Is Sphingosine-1-Phosphate at the Helm?International journal of molecular sciences · 2023Review
- The Role of hsa-miR-125b-5p Interaction with S1P/Ceramide Axis in the Potential Development of Inflammation-Associated Colon Cancer in Primary Sclerosing Cholangitis.International journal of molecular sciences · 2023Article
- The role of sphingosine-1-phosphate in the gut mucosal microenvironment and inflammatory bowel diseases.Frontiers in physiology · 2023Review
- Uncovering the 'sphinx' of sphingosine 1-phosphate signalling: from cellular events to organ morphogenesis.Biological reviews of the Cambridge Philosophical Society · 2022Review
- Atractylenolide III Improves Mitochondrial Function and Protects Against Ulcerative Colitis by Activating AMPK/SIRT1/PGC-1Mediators of inflammation · 2022Article
- Ceramide Metabolism Enzymes-Therapeutic Targets against Cancer.Medicina (Kaunas, Lithuania) · 2021Review
- Targeting Sphingosine-1-Phosphate Signaling in Immune-Mediated Diseases: Beyond Multiple Sclerosis.Drugs · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The bioactive sphingolipid sphingosine-1-phosphate (S1P) and the kinase that produces it have been implicated in inflammatory bowel diseases in mice and humans; however, little is known about the role of the 2 S1P-specific phosphohydrolase isoforms, SGPP1 and SGPP2, which catalyze dephosphorylation of S1P to sphingosine. To elucidate their functions, we generated specific knockout mice. Deletion of Sgpp2, which is mainly expressed in the gastrointestinal tract, significantly reduced dextran sodium sulfate (DSS)-induced colitis severity, whereas deletion of ubiquitously expressed Sgpp1 slightly worsened colitis. Moreover, Sgpp1 deletion enhanced expression of multifunctional proinflammatory cytokines, IL-6, TNF-α, and IL-1β, activation of the transcription factor signal transducer and activator of transcription 3, and immune cell infiltration into the colon. Conversely, Sgpp2-null mice failed to mount a DSS-induced systemic inflammatory response. Of interest, Sgpp2 deficiency suppressed DSS-induced intestinal epithelial cell apoptosis and improved mucosal barrier integrity. Furthermore, down-regulation of Sgpp2 attenuated LPS-induced paracellular permeability in cultured cells and enhanced expression of the adherens junction protein E-cadherin. Finally, in patients with ulcerative colitis, SGPP2 expression was elevated in colitis tissues relative to that in uninvolved tissues. These results indicate that induction of SGPP2 expression contributes to the pathogenesis of colitis by promoting disruption of the mucosal barrier function. SGPP2 may represent a novel therapeutic target in inflammatory bowel disease.-Huang, W.-C., Liang, J., Nagahashi, M., Avni, D., Yamada, A., Maceyka, M., Wolen, A. R., Kordula, T., Milstien, S., Takabe, K., Oravecz, T., Spiegel, S. Sphingosine-1-phosphate phosphatase 2 promotes disruption of mucosal integrity, and contributes to ulcerative colitis in mice and humans.
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Registered trials
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