ArticlePloS one2013
The interaction of endothelin-1 and TGF-β1 mediates vascular cell remodeling.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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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
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 49 citations in OpenAlex.
- Pulmonary hypertension secondary to congenital diaphragmatic hernia: factors and pathways involved in pulmonary vascular remodeling.Pediatric research · 2019Pooled it
- Prostanoid EP₂ Receptors Are Up-Regulated in Human Pulmonary Arterial Hypertension: A Key Anti-Proliferative Target for Treprostinil in Smooth Muscle Cells.International journal of molecular sciences · 2018Trial
- Prophylactic Effects of Combined Bosentan and Nintedanib on Early Post-Traumatic Joint Contracture Formation in a Rat Model.Journal of clinical medicine · 2026Article
- Article
- Role of lipid droplets in pulmonary arterial hypertension: focusing on pulmonary artery smooth muscle cell proliferation.Lipids in health and disease · 2025Review
- Dual Endothelin Receptor Inhibition with Bosentan Does Not Prevent the Early Formation of Post-Traumatic Joint Contracture in a Rat Model.Journal of clinical medicine · 2025Article
- Shifting Shapes: The Endothelial-to-Mesenchymal Transition as a Driver for Cancer Progression.International journal of molecular sciences · 2025Review
- Heterogeneous Cardiac-Derived and Neural Crest-Derived Aortic Smooth Muscle Cells Exhibit Similar Transcriptional Changes After TGFβ Signaling Disruption.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Quercetin regulates pulmonary vascular remodeling in pulmonary hypertension by downregulating TGF-β1-Smad2/3 pathway.BMC cardiovascular disorders · 2024Article
- Circulating Endothelin 1 but Not Transforming Growth Factor-β Levels Are Reduced after Pulmonary Endarterectomy in Subjects Affected by Chronic Thromboembolic Pulmonary Hypertension: A Prospective Cohort Study.Journal of clinical medicine · 2024Article
- The Pathogenesis of Systemic Sclerosis: The Origin of Fibrosis and Interlink with Vasculopathy and Autoimmunity.International journal of molecular sciences · 2023Review
- Review
- Endothelial-to-mesenchymal transition in systemic sclerosis.Clinical and experimental immunology · 2021Review
- Reversal of the Inflammatory Responses in Fabry Patient iPSC-Derived Cardiovascular Endothelial Cells by CRISPR/Cas9-Corrected Mutation.International journal of molecular sciences · 2021Article
- Proinflammation, profibrosis, and arterial aging.Aging medicine (Milton (N.S.W)) · 2020Review
- Transcriptomic modifications in developmental cardiopulmonary adaptations to chronic hypoxia using a murine model of simulated high-altitude exposure.American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Activated Endothelial TGFβ1 Signaling Promotes Venous Thrombus Nonresolution in Mice Via Endothelin-1: Potential Role for Chronic Thromboembolic Pulmonary Hypertension.Circulation research · 2020Article
- Icariin Attenuates Monocrotaline-Induced Pulmonary Arterial Hypertension via the Inhibition of TGF-Evidence-based complementary and alternative medicine : eCAM · 2020Article
- Review
- IgE Downregulates PTEN through MicroRNA-21-5p and Stimulates Airway Smooth Muscle Cell Remodeling.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPulmonary arterial hypertension is characterized by increased thickness of pulmonary vessel walls due to both increased proliferation of pulmonary arterial smooth muscle cell (PASMC) and deposition of extracellular matrix. In patients suffering from pulmonary arterial hypertension, endothelin-1 (ET-1) synthesis is up-regulated and may increase PASMC activity and vessel wall remodeling through transforming growth factor beta-1 (TGF-β1) and connective tissue growth factor.
objectiveTo assess the signaling pathway leading to ET-1 induced proliferation and extracellular matrix deposition by human PASMC.
methodsPASMC were serum starved for 24 hours before stimulation with either ET-1 and/or TGF-β1. ET-1 was inhibited by Bosentan, ERK1/2 mitogen activated protein kinase (MAPK) was inhibited by U0126 and p38 MAPK was inhibited by SB203580.
resultsET-1 increased PASMC proliferation when combined with serum. This effect involved the mitogen activated protein kinases (MAPK) ERK1/2 MAPK and was abrogated by Bosentan which caused a G1- arrest through activation of p27((Kip)). Regarding the contribution of extracellular matrix deposition in vessel wall remodeling, TGF-β1 increased the deposition of collagen type-I and fibronectin, which was further increased when ET-1 was added mainly through ERK1/2 MAPK. In contrast, collagen type-IV was not affected by ET-1. Bosentan dose-dependently reduced the stimulatory effect of ET-1 on collagen type-I and fibronectin, but had no effect on TGF-β1. CONCLUSION AND CLINICAL RELEVANCE: ET-1 alone does not induce PASMC proliferation and extracellular matrix deposition. However, ET-1 significantly up-regulates serum induced proliferation and TGF-β1 induced extracellular matrix deposition, specifically of collagen type-I and fibronectin. The synergistic effects of ET-1 on serum and TGF-β1 involve ERK1/2 MAPK and may thus present a novel mode of action in the pathogenesis of pulmonary arterial hypertension.
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Registered trials
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