ArticleArthritis and rheumatism2011
Amelioration of dermal fibrosis by genetic deletion or pharmacologic antagonism of lysophosphatidic acid receptor 1 in a mouse model of scleroderma.
Article in Arthritis and rheumatism, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 168 citations in OpenAlex.
- Targeting Inflammation in Obesity and the Cardiovascular-Kidney-Metabolic Syndrome Spectrum: A Narrative Review.Obesity facts · 2026Review
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Generation of New Knock-Out Mouse Strains ofInternational journal of molecular sciences · 2025Article
- MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction.The Journal of clinical investigation · 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
- Integration of an LPAR1 Antagonist into Liposomes Enhances Their Internalization and Tumor Accumulation in an Animal Model of Human Metastatic Breast Cancer.Molecular pharmaceutics · 2023Article
- Lysophosphatidic Acid Induces Podocyte Pyroptosis in Diabetic Nephropathy by an Increase of Egr1 Expression via Downregulation of EzH2.International journal of molecular sciences · 2023Article
- Single-cell transcriptome dynamics of the autotaxin-lysophosphatidic acid axis during muscle regeneration reveal proliferative effects in mesenchymal fibro-adipogenic progenitors.Frontiers in cell and developmental biology · 2023Article
- Article
- When natural antibodies become pathogenic: autoantibodies targeted against G protein-coupled receptors in the pathogenesis of systemic sclerosis.Frontiers in immunology · 2023Review
- Ablation of lysophosphatidic acid receptor 1 attenuates hypertrophic cardiomyopathy in a mouse model.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- The LPA-CDK5-tau pathway mediates neuronal injury in an in vitro model of ischemia-reperfusion insult.BMC neurology · 2022Article
- Development of antifibrotic therapy for stricturing Crohn's disease: lessons from randomized trials in other fibrotic diseases.Physiological reviews · 2022Review
- Pharmacokinetics and Metabolism of Ziritaxestat (GLPG1690) in Healthy Male Volunteers Following Intravenous and Oral Administration.Clinical pharmacology in drug development · 2022Article
- Lysophospholipid Mediators in Health and Disease.Annual review of pathology · 2022Review
- The role of antifibrotic therapies in the treatment of systemic sclerosis-associated interstitial lung disease.Therapeutic advances in musculoskeletal disease · 2022Review
- Platelet-derived lysophosphatidic acid mediated LPAR1 activation as a therapeutic target for osteosarcoma metastasis.Oncogene · 2021Article
- The linkage between inflammation and fibrosis in muscular dystrophies: The axis autotaxin-lysophosphatidic acid as a new therapeutic target?Journal of cell communication and signaling · 2021Review
- Role of lysophosphatidic acid and its receptors in health and disease: novel therapeutic strategies.Signal transduction and targeted therapy · 2021Review
- NLRP3 Inflammasome Activation Is Involved in LPAInternational journal of molecular sciences · 2020Article
13 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveScleroderma (systemic sclerosis [SSc]), is characterized by progressive multiorgan fibrosis. We recently implicated lysophosphatidic acid (LPA) in the pathogenesis of pulmonary fibrosis. The purpose of the present study was to investigate the roles of LPA and two of its receptors, LPA₁ and LPA₂, in dermal fibrosis in a mouse model of SSc.
methodsWild type (WT), and LPA₁-knockout (KO) and LPA₂-KO mice were injected subcutaneously with bleomycin or phosphate buffered saline (PBS) once daily for 28 days. Dermal thickness, collagen content, and numbers of cells positive for α-smooth muscle actin (α-SMA) or phospho-Smad2 were determined in bleomycin-injected and PBS-injected skin. In separate experiments, a novel selective LPA₁ antagonist AM095 or vehicle alone was administered by oral gavage to C57BL/6 mice that were challenged with 28 daily injections of bleomycin or PBS. AM095 or vehicle treatments were initiated concurrently with, or 7 or 14 days after, the initiation of bleomycin and PBS injections and continued to the end of the experiments. Dermal thickness and collagen content were determined in injected skin.
resultsThe LPA₁ -KO mice were markedly resistant to bleomycin-induced increases in dermal thickness and collagen content, whereas the LPA₂-KO mice were as susceptible as the WT mice. Bleomycin-induced increases in dermal α-SMA+ and phospho-Smad2+ cells were abrogated in LPA₁-KO mice. Pharmacologic antagonism of LPA₁ with AM095 significantly attenuated bleomycin-induced dermal fibrosis when administered according to either a preventive regimen or two therapeutic regimens.
conclusionThese results suggest that LPA/LPA₁ pathway inhibition has the potential to be an effective new therapeutic strategy for SSc, and that LPA₁ is an attractive pharmacologic target in dermal fibrosis.
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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.