ArticleBiochimica et biophysica acta2015
Prostacyclin post-treatment improves LPS-induced acute lung injury and endothelial barrier recovery via Rap1.
Article in Biochimica et biophysica acta, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 52 citations in OpenAlex.
- Tongjiang Hewei Decoction Improves Airway Hyperresponsiveness in Gastroesophageal Reflux Cough by Inhibiting ADAM33 and Epac1/Rap1 Pathway.Food science & nutrition · 2025Article
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Transcriptomic Biomarkers Associated With Microbiological Etiology and Disease Severity in Childhood Pneumonia.The Journal of infectious diseases · 2025Article
- New Exploration of Therapeutic Targets for Radiation Pneumonitis: Comparative Analysis of Molecular Pathways in Radiation-Induced and LPS-Induced Pneumonitis.International journal of medical sciences · 2025Review
- Rap1A Modulates Store-Operated Calcium Entry in the Lung Endothelium: A Novel Mechanism Controlling NFAT-Mediated Vascular Inflammation and Permeability.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Regulatory effects of the p38 mitogen-activated protein kinase-myosin light chain kinase pathway on the intestinal epithelial mechanical barrier and the mechanism of modified Pulsatilla decoction in the treatment of ulcerative colitis.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024Article
- Designer high-density lipoprotein particles enhance endothelial barrier function and suppress inflammation.Science signaling · 2024Article
- Rap1 in the Context of PCSK9, Atherosclerosis, and Diabetes.Current atherosclerosis reports · 2023Review
- Pulmonary arterial hypertension drugs can partially restore altered angiogenic capacities inPulmonary circulation · 2023Article
- Endothelial mechanisms for inactivation of inflammation-induced hyperpermeability.American journal of physiology. Heart and circulatory physiology · 2023Article
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- Seabuckthorn Berries Extract Attenuates Pulmonary Vascular Hyperpermeability in Lipopolysaccharide-Induced Acute Lung Injury in Mice.Chinese journal of integrative medicine · 2022Article
- ROCK inhibitor fasudil reduces the expression of inflammatory factors in LPS-induced rat pulmonary microvascular endothelial cells via ROS/NF-κB pathway.BMC pharmacology & toxicology · 2022Article
- Epac-2 ameliorates spontaneous colitis in Il-10Journal of cellular and molecular medicine · 2022Article
- Review
- Endothelial Rap1 (Ras-Association Proximate 1) Restricts Inflammatory Signaling to Protect From the Progression of Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Oxidized Phospholipids in Control of Endothelial Barrier Function: Mechanisms and Implication in Lung Injury.Frontiers in endocrinology · 2021Review
- Distinct Signaling Functions of Rap1 Isoforms in NO Release From Endothelium.Frontiers in cell and developmental biology · 2021Article
- [Pathogenic role leukotriene B4 in lung injury induced by lung-protective mechanical ventilation in rabbits].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2020Article
- Luminespib counteracts the Kifunensine-induced lung endothelial barrier dysfunction.Current research in toxicology · 2020Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Protective effects of prostacyclin (PC) or its stable analog beraprost against agonist-induced lung vascular inflammation have been associated with elevation of intracellular cAMP and Rac GTPase signaling which inhibited the RhoA GTPase-dependent pathway of endothelial barrier dysfunction. This study investigated a distinct mechanism of PC-stimulated lung vascular endothelial (EC) barrier recovery and resolution of LPS-induced inflammation mediated by small GTPase Rap1. Efficient barrier recovery was observed in LPS-challenged pulmonary EC after prostacyclin administration even after 15 h of initial inflammatory insult and was accompanied by the significant attenuation of p38 MAP kinase and NFκB signaling and decreased production of IL-8 and soluble ICAM1. These effects were reproduced in cells post-treated with 8CPT, a small molecule activator of Rap1-specific nucleotide exchange factor Epac. By contrast, pharmacologic Epac inhibitor, Rap1 knockdown, or knockdown of cell junction-associated Rap1 effector afadin attenuated EC recovery caused by PC or 8CPT post-treatment. The key role of Rap1 in lung barrier restoration was further confirmed in the murine model of LPS-induced acute lung injury. Lung injury was monitored by measurements of bronchoalveolar lavage protein content, cell count, and Evans blue extravasation and live imaging of vascular leak over 6 days using a fluorescent tracer. The data showed significant acceleration of lung recovery by PC and 8CPT post-treatment, which was abrogated in Rap1a(-/-) mice. These results suggest that post-treatment with PC triggers the Epac/Rap1/afadin-dependent mechanism of endothelial barrier restoration and downregulation of p38MAPK and NFκB inflammatory cascades, altogether leading to accelerated lung recovery.
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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.