ArticleJournal of lipid research2020
Inhibition of sphingosine 1-phosphate lyase activates human keratinocyte differentiation and attenuates psoriasis in mice.
Article in Journal of lipid research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Sphingosine-1-Phosphate and Its Signal Modulators Alleviate Psoriasis-Like Dermatitis: Preclinical and Clinical Evidence and Possible Mechanisms.Frontiers in immunology · 2021Pooled it
- Review
- Effect of Dextran-Aminated Hyaluronic Acid Hydrogel on the Repair of Different Degrees of Epidermal Injury.Journal of cosmetic dermatology · 2025Article
- Inhibition of Sphingosine-1-Phosphate Receptor 2 (S1PBiomolecules & therapeutics · 2025Article
- Epigallocatechin Gallate inPharmaceuticals (Basel, Switzerland) · 2025Article
- Various Cellular Components and Its Signaling Cascades Through the Involvement of Signaling Messengers in Keratinocyte Differentiation.Antioxidants (Basel, Switzerland) · 2025Review
- Contribution of Keratinocytes in Skin Cancer Initiation and Progression.International journal of molecular sciences · 2024Review
- The Role of Alarmins in the Pathogenesis of Rheumatoid Arthritis, Osteoarthritis, and Psoriasis.Current issues in molecular biology · 2024Review
- Promising strategies in natural products treatments of psoriasis-update.Frontiers in medicine · 2024Review
- Targeted siRNA Therapy for Psoriasis: Translating Preclinical Potential into Clinical Treatments.ImmunoTargets and therapy · 2024Review
- Signaling pathways and targeted therapies for psoriasis.Signal transduction and targeted therapy · 2023Review
- Article
- Pathogenic sphingosine 1-phosphate pathway in psoriasis: a critical review of its pathogenic significance and potential as a therapeutic target.Lipids in health and disease · 2023Review
- Ichthyosis linked to sphingosine 1-phosphate lyase insufficiency is due to aberrant sphingolipid and calcium regulation.Journal of lipid research · 2023Article
- Sphingosine 1-Phosphate as Essential Signaling Molecule in Inflammatory Skin Diseases.International journal of molecular sciences · 2023Review
- Crosstalk between pro-survival sphingolipid metabolism and complement signaling induces inflammasome-mediated tumor metastasis.Cell reports · 2022Article
- The Role of Sphingolipids in the Pathogenesis of Psoriasis.Metabolites · 2022Review
- Advances in the pathogenesis of psoriasis: from keratinocyte perspective.Cell death & disease · 2022Review
- A Murine Point Mutation of Sgpl1 Skin Is Enriched With Vγ6 IL17-Producing Cell and Revealed With Hyperpigmentation After Imiquimod Treatment.Frontiers in immunology · 2022Article
- Atopic dermatitis: an expanding therapeutic pipeline for a complex disease.Nature reviews. Drug discovery · 2022Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Sphingosine 1-phosphate (S1P) lyase is an intracellular enzyme that catalyzes the irreversible degradation of S1P and has been suggested as a therapeutic target for the treatment of psoriasis vulgaris. Because S1P induces differentiation of keratinocytes, we examined whether modulation of S1P lyase and altered intracellular S1P levels regulate proliferation and differentiation of human neonatal epidermal keratinocyte (HEKn) cells. To identify the physiological functions of S1P lyase in skin, we inhibited S1P lyase in HEKn cells with an S1P lyase-specific inhibitor (SLI) and with S1P lyase 1 (SGPL1)-specific siRNA (siSGPL1). In HEKn cells, pharmacological treatment with the SLI caused G1 arrest by upregulation of p21 and p27 and induced keratin 1, an early differentiation marker. Similarly, genetic suppression by siSGPL1 arrested the cell cycle at the G1 phase and activated differentiation. In addition, enzyme suppression by siSGPL1 upregulated keratin 1 and differentiation markers including involucrin and loricrin. When hyperproliferation of HEKn cells was induced by interleukin (IL)-17 and IL-22, pharmacologic inhibition of S1P lyase by SLI decreased proliferation and activated differentiation of HEKn cells simultaneously. In addition, SLI administration ameliorated imiquimod-induced psoriatic symptoms including erythema, scaling, and epidermal thickness in vivo. We thus demonstrated that S1P lyase inhibition reduces cell proliferation and induces keratinocyte differentiation, and that inhibition may attenuate psoriasiform changes. Collectively, these findings suggest that S1P lyase is a modulating factor for proliferation and differentiation, and support its potential as a therapeutic target for psoriasis in human keratinocytes.
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