ArticlePloS one2018
Sphingosine-1-phosphate receptor-2 facilitates pulmonary fibrosis through potentiating IL-13 pathway in macrophages.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Molecular Systems Architecture of Fibrotic Lung Microenvironment in Idiopathic Pulmonary Fibrosis.Cells · 2026Pooled it
- Review
- Macrophages and fibroblasts as regulators of the immune response in pancreatic cancer.Nature immunology · 2025Review
- Inhibition of sphingosine 1-phosphate receptor 3 ameliorates bleomycin-induced pulmonary fibrosis by suppressing macrophage M2 polarization.Genes & diseases · 2025Article
- Revisiting pulmonary fibrosis: inflammatory dynamics of the lipofibroblast-to-inflammatory lipofibroblast-to-activated myofibroblast reversible switch.Frontiers in immunology · 2025Review
- SPHK1-mediated M2 macrophage polarization drives TGF-β1-dependent thrombus fibrosis.Frontiers in immunology · 2025Article
- Article
- Sphingosine phosphate lyase insufficiency syndrome as a primary immunodeficiency state.Advances in biological regulation · 2024Review
- Highly Calibrated Relationship Between Bleomycin Concentrations and Facets of the Active Phase Fibrosis in Classical Mouse Bleomycin Model.International journal of molecular sciences · 2024Article
- The novel molecular mechanism of pulmonary fibrosis: insight into lipid metabolism from reanalysis of single-cell RNA-seq databases.Lipids in health and disease · 2024Review
- The functional antagonist of sphingosine-1-phosphate, FTY720, impairs gut barrier function.Frontiers in pharmacology · 2024Article
- A comprehensive multiomics approach reveals that high levels of sphingolipids in cardiac cachexia adipose tissue are associated with inflammatory and fibrotic changes.Lipids in health and disease · 2023Article
- The Role of Macrophages in Connective Tissue Disease-Associated Interstitial Lung Disease: Focusing on Molecular Mechanisms and Potential Treatment Strategies.International journal of molecular sciences · 2023Review
- The Role of Sphingolipids in Regulating Vascular Permeability in Idiopathic Pulmonary Fibrosis.Biomedicines · 2023Review
- STAT6 suppression prevents bleomycin-induced dermal fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- Sphingosine-1-Phosphate Alleviates Irradiation Induced Salivary Gland Hypofunction through Preserving Endothelial Cells and Resident Macrophages.Antioxidants (Basel, Switzerland) · 2022Article
- Modulation of IL-4/IL-13 cytokine signaling in the context of allergic disease.The Journal of allergy and clinical immunology · 2022Review
- Review
- Structure of S1PR2-heterotrimeric GScience advances · 2022Article
- Gut Microbiota, Macrophages and Diet: An Intriguing New Triangle in Intestinal Fibrosis.Microorganisms · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Idiopathic pulmonary fibrosis is a devastating disease with poor prognosis. The pathogenic role of the lysophospholipid mediator sphingosine-1-phosphate and its receptor S1PR2 in lung fibrosis is unknown. We show here that genetic deletion of S1pr2 strikingly attenuated lung fibrosis induced by repeated injections of bleomycin in mice. We observed by using S1pr2LacZ/+ mice that S1PR2 was expressed in alveolar macrophages, vascular endothelial cells and alveolar epithelial cells in the lung and that S1PR2-expressing cells accumulated in the fibrotic legions. Bone marrow chimera experiments suggested that S1PR2 in bone marrow-derived cells contributes to the development of lung fibrosis. Depletion of macrophages greatly attenuated lung fibrosis. Bleomycin administration stimulated the mRNA expression of the profibrotic cytokines IL-13 and IL-4 and the M2 markers including arginase 1, Fizz1/Retnla, Ccl17 and Ccl24 in cells collected from broncho-alveolar lavage fluids (BALF), and S1pr2 deletion markedly diminished the stimulated expression of these genes. BALF cells from bleomycin-administered wild-type mice showed a marked increase in phosphorylation of STAT6, a transcription factor which is activated downstream of IL-13, compared with saline-administered wild-type mice. Interestingly, in bleomycin-administered S1pr2-/- mice, STAT6 phosphorylation in BALF cells was substantially diminished compared with wild-type mice. Finally, pharmacological S1PR2 blockade in S1pr2+/+ mice alleviated bleomycin-induced lung fibrosis. Thus, S1PR2 facilitates lung fibrosis through the mechanisms involving augmentation of IL-13 expression and its signaling in BALF cells, and represents a novel target for treating lung fibrosis.
Indexed as
Identifiers
What OpenQuestion holds
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.