ArticleJournal of cellular physiology2008
Epac/Rap and PKA are novel mechanisms of ANP-induced Rac-mediated pulmonary endothelial barrier protection.
Article in Journal of cellular physiology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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Who cites it
79 citing papers in PubMed, 139 citations in OpenAlex.
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- A PDZ-RapGEF promotes synaptic development in Caenorhabditis elegans through a Rap/Rac signaling pathway.Development (Cambridge, England) · 2025Article
- Prostaglandin EFrontiers in pharmacology · 2025Article
- Molecular Mechanisms Regulating Vascular Endothelial Permeability.International journal of molecular sciences · 2024Review
- Deletion of thePulmonary circulation · 2023Article
- Integrin-Dependent Cell-Matrix Adhesion in Endothelial Health and Disease.Circulation research · 2023Review
- Pleiotropic Roles of Atrial Natriuretic Peptide in Anti-Inflammation and Anti-Cancer Activity.Cancers · 2022Review
- Review
- Binding of the Andes Virus Nucleocapsid Protein to RhoGDI Induces the Release and Activation of the Permeability Factor RhoA.Journal of virology · 2021Article
- Protein kinase A inhibitor proteins (PKIs) divert GPCR-Gαs-cAMP signaling toward EPAC and ERK activation and are involved in tumor growth.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Article
- Extracellular adenosine enhances pulmonary artery vasa vasorum endothelial cell barrier function via Gi/ELMO1/Rac1/PKA-dependent signaling mechanisms.American journal of physiology. Cell physiology · 2020Article
- Small GTPases orchestrate cell-cell communication during collective cell movement.Small GTPases · 2020Review
- Laminin-driven Epac/Rap1 regulation of epithelial barriers on decellularized matrix.Acta biomaterialia · 2019Article
- RhoGTPase in Vascular Disease.Cells · 2019Review
- Mechanosensing and Mechanoregulation of Endothelial Cell Functions.Comprehensive Physiology · 2019Review
- Insights into exchange factor directly activated by cAMP (EPAC) as potential target for cancer treatment.Molecular and cellular biochemistry · 2018Review
- Extracellular adenosine-induced Rac1 activation in pulmonary endothelium: Molecular mechanisms and barrier-protective role.Journal of cellular physiology · 2018Article
- Article
- Protective Effect of Quercetin in LPS-Induced Murine Acute Lung Injury Mediated by cAMP-Epac Pathway.Inflammation · 2018Article
19 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Acute lung injury, sepsis, lung inflammation, and ventilator-induced lung injury are life-threatening conditions associated with lung vascular barrier dysfunction, which may lead to pulmonary edema. Increased levels of atrial natriuretic peptide (ANP) in lung circulation reported in these pathologies suggest its potential role in the modulation of lung injury. Besides well recognized physiological effects on vascular tone, plasma volume, and renal function, ANP may exhibit protective effects in models of lung vascular endothelial cell (EC) barrier dysfunction. However, the molecular mechanisms of ANP protective effects are not well understood. The recently described cAMP-dependent guanine nucleotide exchange factor (GEF) Epac activates small GTPase Rap1, which results in activation of small GTPase Rac-specific GEFs Tiam1 and Vav2 and Rac-mediated EC barrier protective responses. Our results show that ANP stimulated protein kinase A and the Epac/Rap1/Tiam/Vav/Rac cascade dramatically attenuated thrombin-induced pulmonary EC permeability and the disruption of EC monolayer integrity. Using pharmacological and molecular activation and inhibition of cAMP-and cGMP-dependent protein kinases (PKA and PKG), Epac, Rap1, Tiam1, Vav2, and Rac we linked ANP-mediated protective effects to the activation of Epac/Rap and PKA signaling cascades, which dramatically inhibited the Rho pathway of thrombin-induced EC hyper-permeability. These results suggest a novel mechanism of ANP protective effects against agonist-induced pulmonary EC barrier dysfunction via inhibition of Rho signaling by Epac/Rap1-Rac and PKA signaling cascades.
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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.