Trial reportInternational journal of molecular sciences2018
Prostanoid EP₂ Receptors Are Up-Regulated in Human Pulmonary Arterial Hypertension: A Key Anti-Proliferative Target for Treprostinil in Smooth Muscle Cells.
Trial report in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
14 citing papers in PubMed, 33 citations in OpenAlex.
- Simulation of clinical trials of oral treprostinil in pulmonary arterial hypertension using a virtual population.NPJ systems biology and applications · 2025Article
- Inhaled treprostinil in group 3 pulmonary hypertension associated with lung disease: results of the INCREASE and PERFECT studies.Breathe (Sheffield, England) · 2025Article
- Characteristic disease defects in circulating endothelial cells isolated from patients with pulmonary arterial hypertension.PloS one · 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
- Stretch regulates alveologenesis and homeostasis via mesenchymal Gαq/11-mediated TGFβ2 activation.Development (Cambridge, England) · 2023Article
- Antiproliferative effect of selexipag active metabolite MRE-269 on pulmonary arterial smooth muscle cells from patients with chronic thromboembolic pulmonary hypertension.Pulmonary circulation · 2023Article
- Role of prostanoids, nitric oxide and endothelin pathways in pulmonary hypertension due to COPD.Frontiers in medicine · 2023Review
- Imbalanced prostanoid release mediates cigarette smoke-induced human pulmonary artery cell proliferation.Respiratory research · 2022Article
- International Union of Basic and Clinical Pharmacology. CIX. Differences and Similarities between Human and Rodent Prostaglandin EPharmacological reviews · 2020Article
- mTORC1 in Pulmonary Arterial Hypertension. At the Crossroads between Vasoconstriction and Vascular Remodeling?American journal of respiratory and critical care medicine · 2020Article
- Loss of DP1 Aggravates Vascular Remodeling in Pulmonary Arterial Hypertension via mTORC1 Signaling.American journal of respiratory and critical care medicine · 2020Article
- Bronchodilation induced by PGEBritish journal of pharmacology · 2020Article
- Selexipag in the management of pulmonary arterial hypertension: an update.Drug, healthcare and patient safety · 2019Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostacyclins are extensively used to treat pulmonary arterial hypertension (PAH), a life-threatening disease involving the progressive thickening of small pulmonary arteries. Although these agents are considered to act therapeutically via the prostanoid IP receptor, treprostinil is the only prostacyclin mimetic that potently binds to the prostanoid EP₂ receptor, the role of which is unknown in PAH. We hypothesised that EP₂ receptors contribute to the anti-proliferative effects of treprostinil in human pulmonary arterial smooth muscle cells (PASMCs), contrasting with selexipag, a non-prostanoid selective IP agonist. Human PASMCs from PAH patients were used to assess prostanoid receptor expression, cell proliferation, and cyclic adenosine monophosphate (cAMP) levels following the addition of agonists, antagonists or EP₂ receptor small interfering RNAs (siRNAs). Immunohistochemical staining was performed in lung sections from control and PAH patients. We demonstrate using selective IP (RO1138452) and EP₂ (PF-04418948) antagonists that the anti-proliferative actions of treprostinil depend largely on EP₂ receptors rather than IP receptors, unlike MRE-269 (selexipag-active metabolite). Likewise, EP₂ receptor knockdown selectively reduced the functional responses to treprostinil but not MRE-269. Furthermore, EP₂ receptor levels were enhanced in human PASMCs and in lung sections from PAH patients compared to controls. Thus, EP₂ receptors represent a novel therapeutic target for treprostinil, highlighting key pharmacological differences between prostacyclin mimetics used 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.