ArticleMolecular biology of the cell2019
Mechanosensitive Rap1 activation promotes barrier function of lung vascular endothelium under cyclic stretch.
Article in Molecular biology of the cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 27 citations in OpenAlex.
- Hypertensive stretch regulates endothelial cell inflammation and apoptosis through ceramide metabolism.American journal of physiology. Cell physiology · 2026Article
- Targeting Rap1-YAP1 mechanosignaling for ameliorating acute IOP elevation-induced trabecular meshwork dysfunction.iScience · 2026Article
- Plasma Lipidomics Identify Pathways Linked to Acute Lung Injury in a Porcine One-Lung Ventilation Surgery Model.International journal of molecular sciences · 2026Article
- Ventilator-Induced Lung Injury: Mechanotransduction and Potential Therapeutic Targets.MedComm · 2026Review
- Article
- Divergent Functions of Rap1A and Rap1B in Endothelial Biology and Disease.International journal of molecular sciences · 2025Review
- Transcriptomic Biomarkers Associated With Microbiological Etiology and Disease Severity in Childhood Pneumonia.The Journal of infectious diseases · 2025Article
- 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
- Amphipathic Helical Peptide L37pA Protects against Lung Vascular Endothelial Dysfunction Caused by Truncated Oxidized Phospholipids via Antagonism with CD36 Receptor.American journal of respiratory cell and molecular biology · 2024Article
- Mechanisms of endothelial flow sensing.Nature cardiovascular research · 2023Review
- Induction of endothelial barrier dysfunction by serum factors in rats subjected to traumatic brain injury and hemorrhagic shock.Physiological reports · 2022Article
- Microarray Analysis Reveals the Changes in Circular RNA Expression and Molecular Mechanisms in Mice With Ventilator-Induced Lung Injury.Frontiers in physiology · 2022Article
- Mechanotransduction Regulates the Interplays Between Alveolar Epithelial and Vascular Endothelial Cells in Lung.Frontiers in physiology · 2022Review
- CAR Co-Operates With Integrins to Promote Lung Cancer Cell Adhesion and Invasion.Frontiers in oncology · 2022Article
- Perioperative Pulmonary Atelectasis: Part I. Biology and Mechanisms.Anesthesiology · 2022Review
- Nanoparticle delivery of microRNA-146a regulates mechanotransduction in lung macrophages and mitigates injury during mechanical ventilation.Nature communications · 2021Article
- Mechanisms of Mechanical Force Induced Pulmonary Vascular Endothelial Hyperpermeability.Frontiers in physiology · 2021Review
- Signaling diversity enabled by Rap1-regulated plasma membrane ERK with distinct temporal dynamics.eLife · 2020Article
- Modifying and IntegratingFrontiers in bioengineering and biotechnology · 2020Review
- The Importance of Mechanical Forces forFrontiers in physiology · 2020Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Mechanical ventilation remains an imperative treatment for the patients with acute respiratory distress syndrome, but can also exacerbate lung injury. We have previously described a key role of RhoA GTPase in high cyclic stretch (CS)-induced endothelial cell (EC) barrier dysfunction. However, cellular mechanotransduction complexes remain to be characterized. This study tested a hypothesis that recovery of a vascular EC barrier after pathologic mechanical stress may be accelerated by cell exposure to physiologic CS levels and involves Rap1-dependent rearrangement of endothelial cell junctions. Using biochemical, molecular, and imaging approaches we found that EC pre- or postconditioning at physiologically relevant low-magnitude CS promotes resealing of cell junctions disrupted by pathologic, high-magnitude CS. Cytoskeletal remodeling induced by low CS was dependent on small GTPase Rap1. Protective effects of EC preconditioning at low CS were abolished by pharmacological or molecular inhibition of Rap1 activity. In vivo, using mice exposed to mechanical ventilation, we found that the protective effect of low tidal volume ventilation against lung injury caused by lipopolysaccharides and ventilation at high tidal volume was suppressed in Rap1 knockout mice. Taken together, our results demonstrate a prominent role of Rap1-mediated signaling mechanisms activated by low CS in acceleration of lung vascular EC barrier restoration.
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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.