ArticleNature communications2017
TNFα drives pulmonary arterial hypertension by suppressing the BMP type-II receptor and altering NOTCH signalling.
Article in Nature communications, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 148 papers, 2 of them syntheses that pooled it.
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Who cites it
148 citing papers in PubMed, 2 syntheses or guidelines pooled it, 226 citations in OpenAlex.
- Meta-analysis of blood genome-wide expression profiling studies in pulmonary arterial hypertension.American journal of physiology. Lung cellular and molecular physiology · 2020Pooled it
- Genetic determinants of risk in pulmonary arterial hypertension: international genome-wide association studies and meta-analysis.The Lancet. Respiratory medicine · 2019Pooled it
- Beyond the Heart-Lung Axis: A Review of the Crosstalk Between the Hemodynamic, Neurohormonal, and Immune Systems in Pulmonary Hypertension.Comprehensive physiology · 2026Review
- Navigating the Complexity of PH-ILD: From Molecular Mechanisms to Integrated Clinical Evaluation.International journal of molecular sciences · 2026Review
- Interleukin-6 is critical in the development of pulmonary vascular disease inProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Activin Signaling Inhibitors in Pulmonary Hypertension: A State-of-the-Art Review.Pulmonary circulation · 2026Review
- KLF6 activation marks an angiogenic and apoptosis resistant endothelial phenotype in pulmonary arterial hypertension.Communications biology · 2026Article
- Article
- Emerging significance of E3 ubiquitin ligases and Deubiquitinases in pulmonary hypertension.Molecular medicine (Cambridge, Mass.) · 2026Review
- Cellular Signalling Networks in High Altitude Pulmonary Hypertension: From Canonical Pathways to Emerging Targets.Cell proliferation · 2026Review
- Reduction in microbiota-derived short-chain fatty acids contributes to the pathogenesis of pulmonary arterial hypertension.Respiratory research · 2026Article
- A novel explainable deep-learning approach for network analysis of epistatic interactions.NAR genomics and bioinformatics · 2026Article
- Regulation of TGF-β and BMP Signaling by Natural Triterpene Compounds in Pulmonary Arterial Hypertension (PAH).Current issues in molecular biology · 2025Article
- Pathophysiology of Pulmonary Arterial Hypertension: Focus on Vascular Endothelium as a Potential Therapeutic Target.International journal of molecular sciences · 2025Review
- Targeted delivery ofActa pharmaceutica Sinica. B · 2025Article
- Molecular Mechanism of Notch Signaling and Macrophages in Deep Vein Thrombosis: A Comprehensive Review.Cell biochemistry and biophysics · 2025Review
- Comparison of cilomilast, tadalafil, and both drug combinations in the treatment of monocrotaline-induced pulmonary arterial hypertension in rats.BMC cardiovascular disorders · 2025Article
- TNF drives aberrant BMP signaling to induce endothelial and mesenchymal dysregulation in pulmonary hypertension.JCI insight · 2025Article
- C-C Motif chemokine receptor-2 blockade ameliorates pulmonary hypertension in rats and synergizes with a pulmonary vasodilator.Cardiovascular research · 2025Article
- Distinct endothelial cells in chronic thromboembolic pulmonary hypertension.NPJ cardiovascular health · 2025Article
88 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Heterozygous germ-line mutations in the bone morphogenetic protein type-II receptor (BMPR-II) gene underlie heritable pulmonary arterial hypertension (HPAH). Although inflammation promotes PAH, the mechanisms by which inflammation and BMPR-II dysfunction conspire to cause disease remain unknown. Here we identify that tumour necrosis factor-α (TNFα) selectively reduces BMPR-II transcription and mediates post-translational BMPR-II cleavage via the sheddases, ADAM10 and ADAM17 in pulmonary artery smooth muscle cells (PASMCs). TNFα-mediated suppression of BMPR-II subverts BMP signalling, leading to BMP6-mediated PASMC proliferation via preferential activation of an ALK2/ACTR-IIA signalling axis. Furthermore, TNFα, via SRC family kinases, increases pro-proliferative NOTCH2 signalling in HPAH PASMCs with reduced BMPR-II expression. We confirm this signalling switch in rodent models of PAH and demonstrate that anti-TNFα immunotherapy reverses disease progression, restoring normal BMP/NOTCH signalling. Collectively, these findings identify mechanisms by which BMP and TNFα signalling contribute to disease, and suggest a tractable approach for therapeutic intervention in 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.