ArticleThe Journal of biological chemistry2014
Control of vascular permeability by atrial natriuretic peptide via a GEF-H1-dependent mechanism.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 47 citations in OpenAlex.
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- C-type natriuretic peptide preserves central neurological function by maintaining blood-brain barrier integrity.Frontiers in molecular neuroscience · 2022Article
- Molecular Dambusters: What Is Behind Hyperpermeability in Bradykinin-Mediated Angioedema?Clinical reviews in allergy & immunology · 2021Review
- S-1-propenylcysteine improves TNF-α-induced vascular endothelial barrier dysfunction by suppressing the GEF-H1/RhoA/Rac pathway.Cell communication and signaling : CCS · 2021Article
- Microtubules as Major Regulators of Endothelial Function: Implication for Lung Injury.Frontiers in physiology · 2021Review
- Phospholipase D2 restores endothelial barrier function by promoting PTPN14-mediated VE-cadherin dephosphorylation.The Journal of biological chemistry · 2020Article
- Differential role for PAK1 and PAK4 during the invadopodia lifecycle.Small GTPases · 2019Article
- Microtubule destabilization caused by particulate matter contributes to lung endothelial barrier dysfunction and inflammation.Cellular signalling · 2019Article
- Role of truncated oxidized phospholipids in acute endothelial barrier dysfunction caused by particulate matter.PloS one · 2018Article
- Role of End Binding Protein-1 in endothelial permeability response to barrier-disruptive and barrier-enhancing agonists.Cellular signalling · 2017Article
- Regulatory mechanisms, prophylaxis and treatment of vascular leakage following severe trauma and shock.Military Medical Research · 2017Review
- Role of Cingulin in Agonist-induced Vascular Endothelial Permeability.The Journal of biological chemistry · 2016Article
- PAK4 suppresses PDZ-RhoGEF activity to drive invadopodia maturation in melanoma cells.Oncotarget · 2016Article
- The role of atrial natriuretic peptide to attenuate inflammation in a mouse skin wound and individually perfused rat mesenteric microvessels.Physiological reports · 2016Article
- Membrane-anchored proteases in endothelial cell biology.Current opinion in hematology · 2016Review
- Oxidized phospholipids protect against lung injury and endothelial barrier dysfunction caused by heat-inactivated Staphylococcus aureus.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Asef mediates HGF protective effects against LPS-induced lung injury and endothelial barrier dysfunction.American journal of physiology. Lung cellular and molecular physiology · 2015Article
- Hepatocyte growth factor-induced Asef-IQGAP1 complex controls cytoskeletal remodeling and endothelial barrier.The Journal of biological chemistry · 2015Article
- Role of microtubules in attenuation of PepG-induced vascular endothelial dysfunction by atrial natriuretic peptide.Biochimica et biophysica acta · 2015Article
- Atrial natriuretic peptide down-regulates neutrophil recruitment on inflamed endothelium by reducing cell deformability and resistance to detachment force.Biorheology · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Microtubule (MT) dynamics is involved in a variety of cell functions, including control of the endothelial cell (EC) barrier. Release of Rho-specific nucleotide exchange factor GEF-H1 from microtubules activates the Rho pathway of EC permeability. In turn, pathologic vascular leak can be prevented by treatment with atrial natriuretic peptide (ANP). This study investigated a novel mechanism of vascular barrier protection by ANP via modulation of GEF-H1 function. In pulmonary ECs, ANP suppressed thrombin-induced disassembly of peripheral MT and attenuated Rho signaling and cell retraction. ANP effects were mediated by the Rac1 GTPase effector PAK1. Activation of Rac1-PAK1 promoted PAK1 interaction with the Rho activator GEF-H1, inducing phosphorylation of total and MT-bound GEF-H1 and leading to attenuation of Rho-dependent actin remodeling. In vivo, ANP attenuated lung injury caused by excessive mechanical ventilation and TRAP peptide (TRAP/HTV), which was further exacerbated in ANP(-/-) mice. The protective effects of ANP against TRAP/HTV-induced lung injury were linked to the increased pool of stabilized MT and inactivation of Rho signaling via ANP-induced, PAK1-dependent inhibitory phosphorylation of GEF-H1. This study demonstrates a novel protective mechanism of ANP against pathologic hyperpermeability and suggests a novel pharmacological intervention for the prevention of increased vascular leak via PAK1-dependent modulation of GEF-H1 activity.
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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.