ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
Asef mediates HGF protective effects against LPS-induced lung injury and endothelial barrier dysfunction.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- The Artificial-Liver Blood-Purification System Can Effectively Improve Hypercytokinemia for COVID-19.Frontiers in immunology · 2020Trial
- Engineering Extracellular Vesicles Derived from 3D Cultivation of BMSCs Enriched with HGF Ameliorate Sepsis-Induced Lung Epithelial Barrier Damage.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Mechanisms of pulmonary endothelial barrier dysfunction in acute lung injury and acute respiratory distress syndrome.Chinese medical journal pulmonary and critical care medicine · 2024Article
- Biomimetic scaffold-based stem cell transplantation promotes lung regeneration.Bioengineering & translational medicine · 2023Article
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- HGF-Modified Dental Pulp Stem Cells Mitigate the Inflammatory and Fibrotic Responses in Paraquat-Induced Acute Respiratory Distress Syndrome.Stem cells international · 2021Article
- Application of Mesenchymal Stem Cells During Machine Perfusion: An Emerging Novel Strategy for Organ Preservation.Frontiers in immunology · 2021Review
- Microtubules as Major Regulators of Endothelial Function: Implication for Lung Injury.Frontiers in physiology · 2021Review
- Application of Mesenchymal Stem Cells in Inflammatory and Fibrotic Diseases.International journal of molecular sciences · 2020Review
- HGF alleviates septic endothelial injury by inhibiting pyroptosis via the mTOR signalling pathway.Respiratory research · 2020Article
- Critical Role of Mortalin/GRP75 in Endothelial Cell Dysfunction Associated with Acute Lung Injury.Shock (Augusta, Ga.) · 2020Article
- Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier.Stem cells international · 2020Article
- A Novel Microscopic Assay Reveals Heterogeneous Regulation of Local Endothelial Barrier Function.Biophysical journal · 2019Article
- Could Heme Oxygenase-1 Be a New Target for Therapeutic Intervention in Malaria-Associated Acute Lung Injury/Acute Respiratory Distress Syndrome?Frontiers in cellular and infection microbiology · 2018Review
- Mesenchymal stem cells microvesicles stabilize endothelial barrier function partly mediated by hepatocyte growth factor (HGF).Stem cell research & therapy · 2017Article
- Dexmedetomidine mitigates CLP-stimulated acute lung injury via restraining the RAGE pathway.American journal of translational research · 2017Article
- Mesenchymal stem/stromal cells-a key mediator for regeneration after perinatal morbidity?Molecular and cellular pediatrics · 2016Article
- Temporal Profiling of Astrocyte Precursors Reveals Parallel Roles for Asef during Development and after Injury.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- Screening of differentially expressed protein kinases in bone marrow endothelial cells and the protective effects of the p38a inhibitor SB203580 on bone marrow in liver fibrosis.Molecular medicine reports · 2016Article
- Hepatocyte growth factor as a downstream mediator of vascular endothelial growth factor-dependent preservation of growth in the developing lung.American journal of physiology. Lung cellular and molecular physiology · 2016Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Increased vascular endothelial permeability and inflammation are major pathological mechanisms of pulmonary edema and its life-threatening complication, the acute respiratory distress syndrome (ARDS). We have previously described potent protective effects of hepatocyte growth factor (HGF) against thrombin-induced hyperpermeability and identified the Rac pathway as a key mechanism of HGF-mediated endothelial barrier protection. However, anti-inflammatory effects of HGF are less understood. This study examined effects of HGF on the pulmonary endothelial cell (EC) inflammatory activation and barrier dysfunction caused by the gram-negative bacterial pathogen lipopolysaccharide (LPS). We tested involvement of the novel Rac-specific guanine nucleotide exchange factor Asef in the HGF anti-inflammatory effects. HGF protected the pulmonary EC monolayer against LPS-induced hyperpermeability, disruption of monolayer integrity, activation of NF-kB signaling, expression of adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and production of IL-8. These effects were critically dependent on Asef. Small-interfering RNA-induced downregulation of Asef attenuated HGF protective effects against LPS-induced EC barrier failure. Protective effects of HGF against LPS-induced lung inflammation and vascular leak were also diminished in Asef knockout mice. Taken together, these results demonstrate potent anti-inflammatory effects by HGF and delineate a key role of Asef in the mediation of the HGF barrier protective and anti-inflammatory effects. Modulation of Asef activity may have important implications in therapeutic strategies aimed at the treatment of sepsis and acute lung injury/ARDS-induced gram-negative bacterial pathogens.
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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.