ArticleArthritis & rheumatology (Hoboken, N.J.)2016
An Autotaxin/Lysophosphatidic Acid/Interleukin-6 Amplification Loop Drives Scleroderma Fibrosis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 96 citations in OpenAlex.
- Biology and function of the autotaxin/lysophosphatidic acid axis in cancer (Review).Molecular and clinical oncology · 2026Review
- Sex- and Gender-Related Differences in Pruritus in Dermatological Diseases: Insights into Inflammatory, Autoimmune, and Connective Tissue Disorders.Life (Basel, Switzerland) · 2026Review
- Molecular Hydrogen Attenuates Chronic Inflammation and Delays the Onset of Ultraviolet B-Induced Skin Carcinogenesis in Mice.International journal of molecular sciences · 2026Article
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Role of Growth Factors in the Pathogenesis of Systemic-Sclerosis-Associated Fibrosis.International journal of molecular sciences · 2025Review
- The LPAR1 antagonist, PIPE-791 produces antifibrotic effects in models of lung fibrosis.Respiratory research · 2025Article
- Bronchopulmonary dysplasia demonstrates dysregulated autotaxin/lysophosphatidic acid signaling in a neonatal mouse model.Pediatric research · 2025Article
- Psychological stress increases skin infection through the action of TGFβ to suppress immune-acting fibroblasts.Science immunology · 2025Article
- Comparative transcriptomic analysis validates iPSC derived in-vitro progressive fibrosis model as a screening tool for drug discovery and development in systemic sclerosis.Scientific reports · 2024Article
- The Effect of Ionizing Irradiation on the Autotaxin-Lysophasphatidic Acid Axis and Interleukin-6/8 Secretion in Different Breast Cancer Cell Lines.Journal of personalized medicine · 2024Article
- Prediction of Disease Progression and Clinical Response in Systemic Sclerosis: Experience From a Proof-of-Concept Trial.ACR open rheumatology · 2024Article
- Lysophosphatidic acid receptor 1 inhibition: a potential treatment target for pulmonary fibrosis.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Screening Ultra-Large Encoded Compound Libraries Leads to Novel Protein-Ligand Interactions and High Selectivity.Journal of medicinal chemistry · 2024Review
- WTAP boosts lipid oxidation and induces diabetic cardiac fibrosis by enhancing AR methylation.iScience · 2023Article
- Role of Interleukin-6 Family Cytokines in Organ Fibrosis.Kidney diseases (Basel, Switzerland) · 2023Review
- Therapeutic Approaches to Systemic Sclerosis: Recent Approvals and Future Candidate Therapies.Clinical reviews in allergy & immunology · 2023Review
- Emerging roles of lysophosphatidic acid receptor subtype 5 (LPAR5) in inflammatory diseases and cancer.Pharmacology & therapeutics · 2023Review
- Article
- Role of autotaxin in systemic lupus erythematosus.Frontiers in medicine · 2023Review
- A type IV Autotaxin inhibitor ameliorates acute liver injury and nonalcoholic steatohepatitis.EMBO molecular medicine · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
objectiveWe previously implicated the lipid mediator lysophosphatidic acid (LPA) as having a role in dermal fibrosis in systemic sclerosis (SSc). The aim of this study was to identify the role of the LPA-producing enzyme autotaxin (ATX), and to connect the ATX/LPA and interleukin-6 (IL-6) pathways in SSc.
methodsWe evaluated the effect of a novel ATX inhibitor, PAT-048, on fibrosis and IL-6 expression in the mouse model of bleomycin-induced dermal fibrosis. We used dermal fibroblasts from SSc patients and control subjects to evaluate LPA-induced expression of IL-6, and IL-6-induced expression of ATX. We next evaluated whether LPA-induced ATX expression is dependent on IL-6, and whether baseline IL-6 expression in fibroblasts from SSc patients is dependent on ATX. Finally, we compared ATX and IL-6 expression in the skin of patients with SSc and healthy control subjects.
resultsPAT-048 markedly attenuated bleomycin-induced dermal fibrosis when treatment was initiated before or after the development of fibrosis. LPA stimulated expression of IL-6 in human dermal fibroblasts, and IL-6 stimulated fibroblast expression of ATX, connecting the ATX/LPA and IL-6 pathways in an amplification loop. IL-6 knockdown abrogated LPA-induced ATX expression in fibroblasts, and ATX inhibition attenuated IL-6 expression in fibroblasts and the skin of bleomycin-challenged mice. Expression of both ATX and IL-6 was increased in SSc skin, and LPA-induced IL-6 levels and IL-6-induced ATX levels were increased in fibroblasts from SSc patients compared with controls.
conclusionATX is required for the development and maintenance of dermal fibrosis in a mouse model of bleomycin-induced SSc and enables 2 major mediators of SSc fibrogenesis, LPA and IL-6, to amplify the production of each other. Our results suggest that concurrent inhibition of these 2 pathways may be an effective therapeutic strategy for dermal fibrosis in SSc.
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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.