ArticlePhysiological genomics2008
Genomic assessment of a multikinase inhibitor, sorafenib, in a rodent model of pulmonary hypertension.
Article in Physiological genomics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.
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Who cites it
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 119 citations in OpenAlex.
- A Cross-Species and Sex-Specific Meta-Analysis of Transcriptomic Studies of Pulmonary Hypertension.American journal of respiratory cell and molecular biology · 2025Pooled it
- Searching for Old and New Small-Molecule Protein Kinase Inhibitors as Effective Treatments in Pulmonary Hypertension-A Systematic Review.International journal of molecular sciences · 2024Pooled it
- eNAMPT/TLR4 signaling drives PAH cellular phenotypic switching and lung vascular remodeling.Cell communication and signaling : CCS · 2025Article
- PPARγ/ETV2 axis regulates endothelial-to-mesenchymal transition in pulmonary hypertension.Pulmonary circulation · 2024Article
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- Deficiency of the Deubiquitinase UCHL1 Attenuates Pulmonary Arterial Hypertension.Circulation · 2024Article
- Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. FromJournal of Cancer · 2024Article
- Pathophysiological Involvement of Mast Cells and the Lipid Mediators in Pulmonary Vascular Remodeling.International journal of molecular sciences · 2023Review
- Pathophysiology and new advances in pulmonary hypertension.BMJ medicine · 2023Review
- Novel p38 Mitogen-Activated Protein Kinase Inhibitor Reverses Hypoxia-Induced Pulmonary Arterial Hypertension in Rats.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Reversal of pulmonary arterial hypertension and neointimal formation by kinin B1 receptor blockade.Respiratory research · 2021Article
- Zinc-mediated activation of CREB pathway in proliferation of pulmonary artery smooth muscle cells in pulmonary hypertension.Cell communication and signaling : CCS · 2021Article
- Therapeutic Potential of Regorafenib-A Multikinase Inhibitor in Pulmonary Hypertension.International journal of molecular sciences · 2021Article
- Novel Experimental Therapies for Treatment of Pulmonary Arterial Hypertension.Journal of experimental pharmacology · 2021Review
- A proteome signature of umbilical cord serum associated with congenital diaphragmatic hernia.Nagoya journal of medical science · 2020Article
- Divergent changes of p53 in pulmonary arterial endothelial and smooth muscle cells involved in the development of pulmonary hypertension.American journal of physiology. Lung cellular and molecular physiology · 2019Article
- TGF-β and BMPR2 Signaling in PAH: Two Black Sheep in One Family.International journal of molecular sciences · 2018Review
- The aryl hydrocarbon receptor is required for induction of p21cip1/waf1 expression and growth inhibition by SU5416 in hepatoma cells.Oncotarget · 2017Article
- Translational Advances in the Field of Pulmonary Hypertension. From Cancer Biology to New Pulmonary Arterial Hypertension Therapeutics. Targeting Cell Growth and Proliferation Signaling Hubs.American journal of respiratory and critical care medicine · 2017Review
- Microarray analysis in pulmonary hypertension.The European respiratory journal · 2016Review
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Pulmonary hypertension (PH) and cancer pathology share growth factor- and MAPK stress-mediated signaling pathways resulting in endothelial and smooth muscle cell dysfunction and angioproliferative vasculopathy. In this study, we assessed sorafenib, an antineoplastic agent and inhibitor of multiple kinases important in angiogenesis [VEGF receptor (VEGFR)-1-3, PDGF receptor (PDGFR)-beta, Raf-1 kinase] as a potential PH therapy. Two PH rat models were used: a conventional hypoxia-induced PH model and an augmented PH model combining dual VEGFR-1 and -2 inhibition (SU-5416, single 20 mg/kg injection) with hypoxia. In addition to normoxia-exposed control animals, four groups were maintained at 10% inspired O(2) fraction for 3.5 wk (hypoxia/vehicle, hypoxia/SU-5416, hypoxia/sorafenib, and hypoxia/SU-5416/sorafenib). Compared with normoxic control animals, rats exposed to hypoxia/SU-5416 developed hemodynamic and histological evidence of severe PH while rats exposed to hypoxia alone displayed only mild elevations in hemodynamic values (pulmonary vascular and right ventricular pressures). Sorafenib treatment (daily gavage, 2.5 mg/kg) prevented hemodynamic changes and demonstrated dramatic attenuation of PH-associated vascular remodeling. Compared with normoxic control rats, expression profiling (Affymetrix platform) of lung RNA obtained from hypoxia [false discovery rate (FDR) 6.5%]- and hypoxia/SU-5416 (FDR 1.6%)-challenged rats yielded 1,019 and 465 differentially regulated genes (fold change >1.4), respectively. A novel molecular signature consisting of 38 differentially expressed genes between hypoxia/SU-5416 and hypoxia/SU-5416/sorafenib (FDR 6.7%) was validated by either real-time RT-PCR or immunoblotting. Finally, immunoblotting studies confirmed the upregulation of the MAPK cascade in both PH models, which was abolished by sorafenib. In summary, sorafenib represents a novel potential treatment for severe PH with the MAPK cascade a potential canonical target.
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Registered trials
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