ArticlePloS one2012
BMP-9 induced endothelial cell tubule formation and inhibition of migration involves Smad1 driven endothelin-1 production.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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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
28 citing papers in PubMed, 50 citations in OpenAlex.
- Bone morphogenetic protein (BMP)-9, a systemic homeostasis factor with diverse functions in the liver and beyond.Bioscience reports · 2025Review
- Pulmonary hypertension and chronic kidney disease: prevalence, pathophysiology and outcomes.Nature reviews. Nephrology · 2024Review
- An Endothelial Cell Is Not Simply an Endothelial Cell.Stem cells and development · 2024Review
- Pathophysiology in Brain Arteriovenous Malformations: Focus on Endothelial Dysfunctions and Endothelial-to-Mesenchymal Transition.Biomedicines · 2024Review
- ALK1 Signaling in Human Cardiac Progenitor Cells Promotes a Pro-angiogenic Secretome.Journal of cellular signaling · 2024Article
- Endothelial cell SMAD6 balances Alk1 function to regulate adherens junctions and hepatic vascular development.Development (Cambridge, England) · 2023Article
- Endothelial Cell SMAD6 Balances ACVRL1/Alk1 Function to Regulate Adherens Junctions and Hepatic Vascular Development.bioRxiv : the preprint server for biology · 2023Article
- Different cardiovascular and pulmonary phenotypes for single- and double-knock-out mice deficient in BMP9 and BMP10.Cardiovascular research · 2022Article
- Endothelin-1 Upregulates Activin Receptor-Like Kinase-1 Expression via GFrontiers in cardiovascular medicine · 2021Article
- Potential roles of bone morphogenetic protein-9 in glucose and lipid homeostasis.Journal of physiology and biochemistry · 2020Review
- Endothelial protective factors BMP9 and BMP10 inhibit CCL2 release by human vascular endothelial cells.Journal of cell science · 2020Article
- ALK1 signaling in development and disease: new paradigms.Cellular and molecular life sciences : CMLS · 2017Review
- Endothelial follistatin-like-1 regulates the postnatal development of the pulmonary vasculature by modulating BMP/Smad signaling.Pulmonary circulation · 2017Article
- Bromodomain and extra-terminal protein mimic JQ1 decreases inflammation in human vascular endothelial cells: Implications for pulmonary arterial hypertension.Respirology (Carlton, Vic.) · 2017Article
- The Prodomain-Containing BMP9 Produced from a Stable Line Effectively Regulates the Differentiation of Mesenchymal Stem Cells.International journal of medical sciences · 2016Article
- Epigenetic Regulation of GDF2 Suppresses Anoikis in Ovarian and Breast Epithelia.Neoplasia (New York, N.Y.) · 2015Article
- An atypical canonical bone morphogenetic protein (BMP) signaling pathway regulates Msh homeobox 1 (Msx1) expression during odontogenesis.The Journal of biological chemistry · 2014Article
- The role of BMPs in endothelial cell function and dysfunction.Trends in endocrinology and metabolism: TEM · 2014Review
- Potential roles of bone morphogenetic protein (BMP)-9 in human liver diseases.International journal of molecular sciences · 2014Review
- Emerging roles of BMP9 and BMP10 in hereditary hemorrhagic telangiectasia.Frontiers in genetics · 2014Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundBone morphogenetic proteins (BMPs) and their receptors, such as bone morphogenetic protein receptor (BMPR) II, have been implicated in a wide variety of disorders including pulmonary arterial hypertension (PAH). Similarly, endothelin-1 (ET-1), a mitogen and vasoconstrictor, is upregulated in PAH and endothelin receptor antagonists are used in its treatment. We sought to determine whether there is crosstalk between BMP signalling and the ET-1 axis in human pulmonary artery endothelial cells (HPAECs), possible mechanisms involved in such crosstalk and functional consequences thereof. METHODOLOGY/PRINCIPAL FINDING: Using western blot, real time RT-PCR, ELISA and small RNA interference methods we provide evidence that in HPAECs BMP-9, but not BMP-2, -4 and -6 significantly stimulated ET-1 release under physiological concentrations. This release is mediated by both Smad1 and p38 MAPK and is independent of the canonical Smad4 pathway. Moreover, knocking down the ALK1 receptor or BMPR II attenuates BMP-9 stimulated ET-1 release, whilst causing a significant increase in prepro ET-1 mRNA transcription and mature peptide release. Finally, BMP-9 induced ET-1 release is involved in both inhibition of endothelial cell migration and promotion of tubule formation. CONCLUSIONS/SIGNIFICANCE: Although our data does not support an important role for BMP-9 as a source of increased endothelial ET-1 production seen in human PAH, BMP-9 stimulated ET-1 production is likely to be important in angiogenesis and vascular stability. However, increased ET-1 production by endothelial cells as a consequence of BMPR II dysfunction may be clinically relevant in the pathogenesis of PAH.
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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.