ArticleThe Journal of biological chemistry2008
Prostaglandin E2-activated Epac promotes neointimal formation of the rat ductus arteriosus by a process distinct from that of cAMP-dependent protein kinase A.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
36 citing papers in PubMed, 72 citations in OpenAlex.
- The update of prostaglandin E2 receptor subtype 4 (EP4) in inflammatory diseases.Genes & diseases · 2026Review
- High PGEScientifica · 2026Article
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Keeping the Ductus Arteriosus Patent: Current Strategy and Perspectives.Diagnostics (Basel, Switzerland) · 2025Review
- Role of EP4 factor in paediatric type 1 diabetes mellitus: a comprehensive review focusing on the honeymoon period.Pediatric endocrinology, diabetes, and metabolism · 2024Review
- A novel role for PGEAmerican journal of physiology. Heart and circulatory physiology · 2023Article
- Mouse models of patent ductus arteriosus (PDA) and their relevance for human PDA.Developmental dynamics : an official publication of the American Association of Anatomists · 2022Review
- Transcriptome Analysis Reveals Differential Gene Expression between the Closing Ductus Arteriosus and the Patent Ductus Arteriosus in Humans.Journal of cardiovascular development and disease · 2021Article
- EPAC in Vascular Smooth Muscle Cells.International journal of molecular sciences · 2020Review
- Role of Tissue-Type Plasminogen Activator in Remodeling of the Ductus Arteriosus.Circulation reports · 2020Review
- Review
- Review
- Epac1 deficiency inhibits basic fibroblast growth factor-mediated vascular smooth muscle cell migration.The journal of physiological sciences : JPS · 2019Article
- Synergistic effect of phosphodiesterase 4 inhibitor and serum on migration of endotoxin-stimulated macrophages.Innate immunity · 2018Article
- Molecular Mechanisms for Regulating Postnatal Ductus Arteriosus Closure.International journal of molecular sciences · 2018Review
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- Extracellular polysaccharides purified from Aureobasidium pullulans SM‑2001 (Polycan) inhibit dexamethasone‑induced muscle atrophy in mice.International journal of molecular medicine · 2018Article
- Tissue-type plasminogen activator contributes to remodeling of the rat ductus arteriosus.PloS one · 2018Article
- Epac activation inhibits IL-6-induced cardiac myocyte dysfunction.The journal of physiological sciences : JPS · 2018Article
- Attenuation of ductus arteriosus intimal thickening in preterm sheep twins compared with singletons.The journal of physiological sciences : JPS · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
We have demonstrated that chronic stimulation of the prostaglandin E2-cAMP-dependent protein kinase A (PKA) signal pathway plays a critical role in intimal cushion formation in perinatal ductus arteriosus (DA) through promoting synthesis of hyaluronan. We hypothesized that Epac, a newly identified effector of cAMP, may play a role in intimal cushion formation (ICF) in the DA distinct from that of PKA. In the present study, we found that the levels of Epac1 and Epac2 mRNAs were significantly up-regulated in the rat DA during the perinatal period. A specific EP4 agonist, ONO-AE1-329, increased Rap1 activity in the presence of a PKA inhibitor, PKI-(14-22)-amide, in DA smooth muscle cells. 8-pCPT-2'-O-Me-cAMP (O-Me-cAMP), a cAMP analog selective to Epac activator, promoted migration of DA smooth muscle cells (SMC) in a dose-dependent manner. Adenovirus-mediated Epac1 or Epac2 gene transfer further enhanced O-Me-cAMP-induced cell migration, although the effect of Epac1 overexpression on cell migration was stronger than that of Epac2. In addition, transfection of small interfering RNAs for Epac1, but not Epac2, significantly inhibited serum-mediated migration of DA SMCs. In the presence of O-Me-cAMP, actin stress fibers were well organized with enhanced focal adhesion, and cell shape was widely expanded. Adenovirus-mediated Epac1, but not Epac2 gene transfer, induced prominent ICF in the rat DA explants when compared with those with green fluorescent protein gene transfer. The thickness of intimal cushion became significantly greater (1.98-fold) in Epac1-overexpressed DA. O-Me-cAMP did not change hyaluronan production, although it decreased proliferation of DA SMCs. The present study demonstrated that Epac, especially Epac1, plays an important role in promoting SMC migration and thereby ICF in the rat DA.
Indexed as
Identifiers
What OpenQuestion holds
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.