ArticleThe Journal of biological chemistry2009
Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 125 papers.
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Who cites it
125 citing papers in PubMed, 212 citations in OpenAlex.
- FKBP12 determines ligand-specific SMAD signaling in individual living endothelial cells.iScience · 2026Article
- Article
- Bone Morphogenetic Protein (BMP) 9 Outperforms BMP2 in Osteogenesis and Osseointegration: In Vitro and In Vivo.Clinical implant dentistry and related research · 2026Article
- Article
- Advances in Novel Therapeutic Strategies for Pulmonary Arterial Hypertension.Canadian respiratory journal · 2026Review
- Endoglin as a BMP9 co-receptor in vascular endothelial cells: prodomain displacement and TGFBRII recruitment.Nature communications · 2025Article
- Disrupting BMP/TGF-β Signaling: Modulation of AQP1 and TGFB1 in Human Pulmonary Microvascular Endothelial Cells.Comprehensive Physiology · 2025Article
- Bmpr2 Loss in the Vascular Endothelium Enhances Neoangiogenesis and Growth of Lung Metastatic Lesions in a Mouse Model of Breast Cancer.Journal of cellular biochemistry · 2025Article
- BMP9 regulates the endothelial secretome to drive pulmonary hypertension.bioRxiv : the preprint server for biology · 2025Article
- Signaling pathways and targeted therapy for pulmonary hypertension.Signal transduction and targeted therapy · 2025Review
- Activin-A Regulates Bone Morphogenetic Protein Signaling in Pulmonary Endothelial Cells Without Affecting Bone Morphogenetic Protein Type-II Receptor Expression.Pulmonary circulation · 2025Article
- ActRII or BMPR ligands inhibit skeletal myoblast differentiation, and BMPs promote heterotopic ossification in skeletal muscles in mice.Skeletal muscle · 2025Article
- Pulmonary Arterial Hypertension and TGF-β Superfamily Signaling: Focus on Sotatercept.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2024Review
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- Unveiling the Impact of BMP9 in Liver Diseases: Insights into Pathogenesis and Therapeutic Potential.Biomolecules · 2024Review
- Effects of Modulating BMP9, BMPR2, and AQP1 on BMP Signaling in Human Pulmonary Microvascular Endothelial Cells.International journal of molecular sciences · 2024Article
- Bone morphogenetic protein signalling in pulmonary arterial hypertension: revisiting the BMPRII connection.Biochemical Society transactions · 2024Review
- Article
- Characteristic disease defects in circulating endothelial cells isolated from patients with pulmonary arterial hypertension.PloS one · 2024Article
- AFrontiers in cardiovascular medicine · 2024Article
65 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
Mutations in transforming growth factor-beta (TGF-beta) receptor superfamily members underlie conditions characterized by vascular dysplasia. Mutations in endoglin and activin-like kinase receptor 1 (ALK1) cause hereditary hemorrhagic telangiectasia, whereas bone morphogenetic protein type II receptor (BMPR-II) mutations underlie familial pulmonary arterial hypertension. To understand the functional roles of these receptors, we examined their relative contributions to BMP signaling in human pulmonary artery endothelial cells (HPAECs). BMP9 potently and selectively induced Smad1/5 phosphorylation and Id gene expression in HPAECs. Contrary to expectations, BMP9 also stimulated Smad2 activation. Furthermore, BMP9 induced the expression of interleukin 8 and E-selectin. Using small interfering RNA, we demonstrate that the type I receptor, ALK1, is essential for these responses. However, small interfering RNA and inhibitor studies showed no involvement of ALK5 or endoglin. We further demonstrate that, of the candidate type II receptors, BMPR-II predominantly mediated IL-8 and E-selectin induction and mitogenic inhibition by BMP9. Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation. Only abolition of both type II receptors significantly reduced the Smad1/5 and Id responses. Both ALK1 and BMPR-II contributed to growth inhibition of HPAECs, whereas ActR-II was not involved. Taken together, our findings demonstrate the critical role of type II receptors in balancing BMP9 signaling via ALK1 and emphasize the essential role for BMPR-II in a subset of BMP9 responses (interleukin 8, E-selectin, and proliferation). This differential signaling may contribute to the contrasting pathologies of hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension.
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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.