ArticleThe Journal of clinical investigation2016
Placenta growth factor augments airway hyperresponsiveness via leukotrienes and IL-13.
Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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Who cites it
22 citing papers in PubMed, 34 citations in OpenAlex.
- The multifaceted role of placental growth factor in the pathogenesis and progression of bronchial asthma and pulmonary fibrosis: Therapeutic implications.Genes & diseases · 2023Review
- Impact of hydroxyurea on lymphocyte subsets in children with sickle cell anemia.Pediatric research · 2023Article
- The Role of Inflammation in The Cellular and Molecular Mechanisms of Cardiopulmonary Complications of Sickle Cell Disease.Biomolecules · 2023Review
- Airway hyperresponsiveness development and the toxicity of PM2.5.Environmental science and pollution research international · 2021Review
- Genetic modifiers of long-term survival in sickle cell anemia.Clinical and translational medicine · 2020Article
- The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease.Frontiers in immunology · 2020Review
- Cardiac expression of HMOX1 and PGF in sickle cell mice and haem-treated wild type mice dominates organ expression profiles via Nrf2 (Nfe2l2).British journal of haematology · 2019Article
- Free heme regulates placenta growth factor through NRF2-antioxidant response signaling.Free radical biology & medicine · 2019Article
- Airway Inflammation and Lung Function in Sickle Cell Disease.Pediatric allergy, immunology, and pulmonology · 2019Article
- Identifying Clinical and Research Priorities in Sickle Cell Lung Disease. An Official American Thoracic Society Workshop Report.Annals of the American Thoracic Society · 2019Article
- Therapeutic strategies for sickle cell disease: towards a multi-agent approach.Nature reviews. Drug discovery · 2019Review
- Aeroallergen sensitization predicts acute chest syndrome in children with sickle cell anaemia.British journal of haematology · 2018Article
- Protective Effects of Casticin FromFrontiers in pharmacology · 2018Article
- Placenta growth factor mediated gene regulation in sickle cell disease.Blood reviews · 2018Review
- Leukotrienes and sex: strange bedfellows?The Journal of clinical investigation · 2017Article
- Outstanding animal studies in allergy I. From asthma to food allergy and anaphylaxis.Current opinion in allergy and clinical immunology · 2017Review
- Airway Hyperresponsiveness Does Not Predict Morbidity in Children with Sickle Cell Anemia.American journal of respiratory and critical care medicine · 2017Article
- Developing new pharmacotherapeutic approaches to treating sickle-cell disease.ISBT science series · 2017Article
- Neutrophilic Inflammation in the Immune Responses of Chronic Obstructive Pulmonary Disease: Lessons from Animal Models.Journal of immunology research · 2017Review
- Placental growth factor: What hematologists need to know.Blood reviews · 2017Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Airway hyperresponsiveness (AHR) affects 55%-77% of children with sickle cell disease (SCD) and occurs even in the absence of asthma. While asthma increases SCD morbidity and mortality, the mechanisms underlying the high AHR prevalence in a hemoglobinopathy remain unknown. We hypothesized that placenta growth factor (PlGF), an erythroblast-secreted factor that is elevated in SCD, mediates AHR. In allergen-exposed mice, loss of Plgf dampened AHR, reduced inflammation and eosinophilia, and decreased expression of the Th2 cytokine IL-13 and the leukotriene-synthesizing enzymes 5-lipoxygenase and leukotriene-C4-synthase. Plgf-/- mice treated with leukotrienes phenocopied the WT response to allergen exposure; conversely, anti-PlGF Ab administration in WT animals blunted the AHR. Notably, Th2-mediated STAT6 activation further increased PlGF expression from lung epithelium, eosinophils, and macrophages, creating a PlGF/leukotriene/Th2-response positive feedback loop. Similarly, we found that the Th2 response in asthma patients is associated with increased expression of PlGF and its downstream genes in respiratory epithelial cells. In an SCD mouse model, we observed increased AHR and higher leukotriene levels that were abrogated by anti-PlGF Ab or the 5-lipoxygenase inhibitor zileuton. Overall, our findings indicate that PlGF exacerbates AHR and uniquely links the leukotriene and Th2 pathways in asthma. These data also suggest that zileuton and anti-PlGF Ab could be promising therapies to reduce pulmonary morbidity in SCD.
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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.