ArticleThe Journal of clinical investigation2015
EP3 receptor deficiency attenuates pulmonary hypertension through suppression of Rho/TGF-β1 signaling.
Article in The Journal of clinical investigation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 78 citations in OpenAlex.
- G Protein-Coupled Receptor in High-Altitude Diseases: Mechanistic Insights and Therapeutic Opportunities.MedComm · 2026Review
- Article
- Disrupting BMP/TGF-β Signaling: Modulation of AQP1 and TGFB1 in Human Pulmonary Microvascular Endothelial Cells.Comprehensive Physiology · 2025Article
- Genome-wide characterization of circular RNAs in three rat models of pulmonary hypertension reveals distinct pathological patterns.BMC genomics · 2025Article
- Biomarkers in COPD-Associated PH/CCP: Circulating Molecules and Cell-Intrinsic Marker.International journal of chronic obstructive pulmonary disease · 2025Review
- Microscopy Image Dataset for Deep Learning-Based Quantitative Assessment of Pulmonary Vascular Changes.Scientific data · 2024Article
- Disease-associated gut microbiome and metabolome changes in rats with chronic hypoxia-induced pulmonary hypertension.Frontiers in cell and developmental biology · 2024Article
- The Emerging Therapeutic Role of Prostaglandin E2 Signaling in Pulmonary Hypertension.Metabolites · 2023Review
- Prostaglandin and prostaglandin receptors: present and future promising therapeutic targets for pulmonary arterial hypertension.Respiratory research · 2023Review
- UGCG modulates heart hypertrophy through B4GalT5-mediated mitochondrial oxidative stress and the ERK signaling pathway.Cellular & molecular biology letters · 2023Article
- Article
- The Evolving Management and Treatment Options for Patients with Pulmonary Hypertension: Current Evidence and Challenges.Vascular health and risk management · 2023Review
- Total flavones fromAnnals of translational medicine · 2022Article
- Group 3 Pulmonary Hypertension: From Bench to Bedside.Circulation research · 2022Review
- EP3 Receptor Deficiency Improves Vascular Remodeling and Cognitive Impairment in Cerebral Small Vessel Disease.Aging and disease · 2022Article
- Leflunomide-induced pulmonary arterial hypertension in a young man with nephrotic syndrome: A case report.Frontiers in pharmacology · 2022Article
- Roles of EP Receptors in the Regulation of Fluid Balance and Blood Pressure.Frontiers in endocrinology · 2022Review
- Fibroblast-specific activation of Rnd3 protects against cardiac remodeling in diabetic cardiomyopathy via suppression of Notch and TGF-β signaling.Theranostics · 2022Article
- Review
- Pharmacological blockade of the EP3 prostaglandin EMolecular metabolism · 2021Article
Corrections and comments
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Authors and funding
25 authors at 7 institutions in 4 countries.
Funding
Abstract
Pulmonary arterial hypertension (PAH) is commonly associated with chronic hypoxemia in disorders such as chronic obstructive pulmonary disease (COPD). Prostacyclin analogs are widely used in the management of PAH patients; however, clinical efficacy and long-term tolerability of some prostacyclin analogs may be compromised by concomitant activation of the E-prostanoid 3 (EP3) receptor. Here, we found that EP3 expression is upregulated in pulmonary arterial smooth muscle cells (PASMCs) and human distal pulmonary arteries (PAs) in response to hypoxia. Either pharmacological inhibition of EP3 or Ep3 deletion attenuated both hypoxia and monocrotaline-induced pulmonary hypertension and restrained extracellular matrix accumulation in PAs in rodent models. In a murine PAH model, Ep3 deletion in SMCs, but not endothelial cells, retarded PA medial thickness. Knockdown of EP3α and EP3β, but not EP3γ, isoforms diminished hypoxia-induced TGF-β1 activation. Expression of either EP3α or EP3β in EP3-deficient PASMCs restored TGF-β1 activation in response to hypoxia. EP3α/β activation in PASMCs increased RhoA-dependent membrane type 1 extracellular matrix metalloproteinase (MMP) translocation to the cell surface, subsequently activating pro-MMP-2 and promoting TGF-β1 signaling. Activation or disruption of EP3 did not influence PASMC proliferation. Together, our results indicate that EP3 activation facilitates hypoxia-induced vascular remodeling and pulmonary hypertension in mice and suggest EP3 inhibition as a potential therapeutic strategy for pulmonary 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.