ArticleThe Journal of clinical investigation2017
Autocrine lysophosphatidic acid signaling activates β-catenin and promotes lung allograft fibrosis.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 61 citations in OpenAlex.
- Single-cell multiomic analysis of mesenchymal cells reveals molecular signatures and regulators of lung allograft fibrosis.JCI insight · 2026Article
- IOA-244, a novel p110δ PI3K inhibitor, blocks breast tumour progression on either mono- or combined-therapy.Cell death discovery · 2026Article
- LPAR1 Promotes Activation of Pathways Alveolar Hypercoagulation and Fibrinolytic Inhibition in ARDS via NF-κB Signaling Pathway.FASEB bioAdvances · 2025Article
- MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction.The Journal of clinical investigation · 2024Article
- Review
- Lysophosphatidic Acid-Mediated Inflammation at the Heart of Heart Failure.Current cardiology reports · 2024Review
- A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer.Communications biology · 2024Article
- Genetic deficiency of the transcription factor NFAT1 confers protection against fibrogenic responses independent of immune influx.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- Orai3 mediates Orai channel remodelling to activate fibroblast in pulmonary fibrosis.Journal of cellular and molecular medicine · 2022Article
- Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model.Molecular therapy oncolytics · 2022Article
- LncRNAActa pharmaceutica Sinica. B · 2022Article
- Tumor-Derived Lysophosphatidic Acid Blunts Protective Type I Interferon Responses in Ovarian Cancer.Cancer discovery · 2022Article
- Autotaxin/Lysophosphatidic Acid Axis: From Bone Biology to Bone Disorders.International journal of molecular sciences · 2022Review
- Transcription factor FOXF1 identifies compartmentally distinct mesenchymal cells with a role in lung allograft fibrogenesis.The Journal of clinical investigation · 2021Article
- Interleukin 6 trans-signaling is a critical driver of lung allograft fibrosis.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2021Article
- Emerging drug delivery strategies for idiopathic pulmonary fibrosis treatment.European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V · 2021Review
- Review
- Loss of FOXF1 expression promotes human lung-resident mesenchymal stromal cell migration via ATX/LPA/LPA1 signaling axis.Scientific reports · 2020Article
- Humoral immune responses mediate the development of a restrictive phenotype of chronic lung allograft dysfunction.JCI insight · 2020Article
- Latest progress on the molecular mechanisms of idiopathic pulmonary fibrosis.Molecular biology reports · 2020Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Tissue fibrosis is the primary cause of long-term graft failure after organ transplantation. In lung allografts, progressive terminal airway fibrosis leads to an irreversible decline in lung function termed bronchiolitis obliterans syndrome (BOS). Here, we have identified an autocrine pathway linking nuclear factor of activated T cells 2 (NFAT1), autotaxin (ATX), lysophosphatidic acid (LPA), and β-catenin that contributes to progression of fibrosis in lung allografts. Mesenchymal cells (MCs) derived from fibrotic lung allografts (BOS MCs) demonstrated constitutive nuclear β-catenin expression that was dependent on autocrine ATX secretion and LPA signaling. We found that NFAT1 upstream of ATX regulated expression of ATX as well as β-catenin. Silencing NFAT1 in BOS MCs suppressed ATX expression, and sustained overexpression of NFAT1 increased ATX expression and activity in non-fibrotic MCs. LPA signaling induced NFAT1 nuclear translocation, suggesting that autocrine LPA synthesis promotes NFAT1 transcriptional activation and ATX secretion in a positive feedback loop. In an in vivo mouse orthotopic lung transplant model of BOS, antagonism of the LPA receptor (LPA1) or ATX inhibition decreased allograft fibrosis and was associated with lower active β-catenin and dephosphorylated NFAT1 expression. Lung allografts from β-catenin reporter mice demonstrated reduced β-catenin transcriptional activation in the presence of LPA1 antagonist, confirming an in vivo role for LPA signaling in β-catenin activation.
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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.