ArticleThe Journal of biological chemistry2010
Placenta growth factor (PlGF), a novel inducer of plasminogen activator inhibitor-1 (PAI-1) in sickle cell disease (SCD).
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- Heme-bound iron activates placenta growth factor in erythroid cells via erythroid Krüppel-like factor.Blood · 2014Trial
- AP1 Transcription Factor in the Regulation of the Urokinase Plasminogen Activation System.Biomolecules · 2026Review
- Systematic Review of Non-Coding Genomic Variants in Globin and Non-Globin Clusters and Their Impact on Phenotypic Severity in Thalassemia and Sickle Cell Disease.Journal of clinical medicine · 2026Review
- Correlation Between Von Willebrand Factor, Thrombin-Antithrombin Complex, and Disease Severity in Sickle Cell Disease: Implications for Thrombosis.Journal of blood medicine · 2026Article
- Inflammation and autoimmunity are interrelated in patients with sickle cell disease at a steady-state condition: implications for vaso-occlusive crisis, pain, and sensory sensitivity.Frontiers in immunology · 2024Article
- Endothelial dysfunction biomarkers in sickle cell disease: is there a role for ADMA and PAI-1?Annals of hematology · 2022Article
- Hydroxyurea improves nitric oxide bioavailability in humanized sickle cell mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- The Worst Things in Life are Free: The Role of Free Heme in Sickle Cell Disease.Frontiers in immunology · 2020Review
- Inflammation in sickle cell disease.Clinical hemorheology and microcirculation · 2018Article
- Placenta growth factor mediated gene regulation in sickle cell disease.Blood reviews · 2018Review
- Article
- Activated Transcription Factor 3 in Association with Histone Deacetylase 6 Negatively Regulates MicroRNA 199a2 Transcription by Chromatin Remodeling and Reduces Endothelin-1 Expression.Molecular and cellular biology · 2016Article
- Placenta growth factor augments airway hyperresponsiveness via leukotrienes and IL-13.The Journal of clinical investigation · 2016Article
- Peroxisome proliferator-activated receptor-α-mediated transcription of miR-301a and miR-454 and their host gene SKA2 regulates endothelin-1 and PAI-1 expression in sickle cell disease.Bioscience reports · 2015Article
- Erythropoietin-mediated expression of placenta growth factor is regulated via activation of hypoxia-inducible factor-1α and post-transcriptionally by miR-214 in sickle cell disease.The Biochemical journal · 2015Article
- PEDF and its roles in physiological and pathological conditions: implication in diabetic and hypoxia-induced angiogenic diseases.Clinical science (London, England : 1979) · 2015Review
- Key endothelial cell angiogenic mechanisms are stimulated by the circulating milieu in sickle cell disease and attenuated by hydroxyurea.Haematologica · 2015Article
- MicroRNA 648 Targets ET-1 mRNA and is cotranscriptionally regulated with MICAL3 by PAX5.Molecular and cellular biology · 2015Article
- Peroxisome proliferator-activated receptor-α-mediated transcription of miR-199a2 attenuates endothelin-1 expression via hypoxia-inducible factor-1α.The Journal of biological chemistry · 2014Article
- Ironing out placenta growth factor.Blood · 2014Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Sickle cell disease (SCD) is characterized by a prothrombotic state. Plasminogen activator inhibitor-1 (PAI-1) is known to modulate fibrinolysis, lung injury/fibrosis, and angiogenesis. However, its role in SCD is less understood, and the molecular mechanisms underlying increased PAI-1 are unknown. Herein, we show a novel link between PAI-1 and sickle erythropoiesis. Plasma PAI-1 levels were high in SCD patients at steady state and in two humanized sickle mouse models, with increased PAI-1 immunolabeling in sickle mouse lung, bronchial epithelial cells, alveolar macrophages, and pulmonary microvascular endothelial cells. Placenta growth factor (PlGF), released at high levels by sickle erythroblasts, induced PAI-1 expression in primary human pulmonary microvascular endothelial cells and monocytes through activation of c-Jun N-terminal kinase (JNK), NADPH oxidase, and hypoxia-inducible factor-1alpha (HIF-1alpha). Analysis of the human PAI-1 promoter revealed this induction was mediated by hypoxia-response element (HRE)-1, HRE-2, and distal activator protein (AP-1) sites. We also identify the involvement of c-Jun, c-Jun/c-Fos, and JunD, but not JunB, in binding with AP-1 sites of the PAI-1 promoter upon PlGF induction. Consistent with these findings, levels of PAI-1 were low in PlGF knock-out mice and sickle-PlGF knock-out mice; overexpression of PlGF in normal mice increased circulating PAI-1. In conclusion, we identify a novel mechanism of PAI-1 elevation 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.