ArticlePloS one2014
Stiffness-activated GEF-H1 expression exacerbates LPS-induced lung inflammation.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Lysyl Oxidase Promotes Actin-Dependent Neutrophil Activation and Cytotoxicity Toward Retinal Endothelial Cells in Diabetes.Diabetes · 2026Article
- LPS exacerbates TRPV4-mediated itch through the intracellular TLR4-PI3K signalling.Journal of cellular and molecular medicine · 2024Article
- SIRT6 Protects Against Lipopolysaccharide-Induced Inflammation in Human Pulmonary Lung Microvascular Endothelial Cells.Inflammation · 2024Article
- Article
- Stiffness-induced modulation of ERG transcription factor in chronic liver disease.Npj gut and liver · 2024Article
- Mechanobiology of portal hypertension.JHEP reports : innovation in hepatology · 2023Review
- Subendothelial Matrix Stiffening by Lysyl Oxidase Enhances RAGE-Mediated Retinal Endothelial Activation in Diabetes.Diabetes · 2023Article
- A novel pulmonary fibrosis murine model with immune-related liver injury.Animal models and experimental medicine · 2023Article
- Therapeutic Validation of GEF-H1 Using a De Novo Designed Inhibitor in Models of Retinal Disease.Cells · 2022Article
- Endothelial inflammation and neutrophil transmigration are modulated by extracellular matrix composition in an inflammation-on-a-chip model.Scientific reports · 2022Article
- Mechanobiology of Pulmonary Diseases: A Review of Engineering Tools to Understand Lung Mechanotransduction.Journal of biomechanical engineering · 2021Review
- Influence of Culture Substrates on Morphology and Function of Pulmonary Alveolar Cells In Vitro.Biomolecules · 2021Article
- Microtubules as Major Regulators of Endothelial Function: Implication for Lung Injury.Frontiers in physiology · 2021Review
- Mechanical forces and metabolic changes cooperate to drive cellular memory and endothelial phenotypes.Current topics in membranes · 2021Review
- Lysyl Oxidase (LOX): Functional Contributions to Signaling Pathways.Biomolecules · 2020Review
- Integrating Biophysics in Toxicology.Cells · 2020Review
- Cells under stress: The mechanical environment shapes inflammasome responses to danger signals.Journal of leukocyte biology · 2019Review
- Mechanosensing and Mechanoregulation of Endothelial Cell Functions.Comprehensive Physiology · 2019Review
- Endothelial Cell Mechano-Metabolomic Coupling to Disease States in the Lung Microvasculature.Frontiers in bioengineering and biotechnology · 2019Review
- Extracellular matrix in lung development, homeostasis and disease.Matrix biology : journal of the International Society for Matrix Biology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Acute lung injury (ALI) is accompanied by decreased lung compliance. However, a role of tissue mechanics in modulation of inflammation remains unclear. We hypothesized that bacterial lipopolysacharide (LPS) stimulates extracellular matrix (ECM) production and vascular stiffening leading to stiffness-dependent exacerbation of endothelial cell (EC) inflammatory activation and lung barrier dysfunction. Expression of GEF-H1, ICAM-1, VCAM-1, ECM proteins fibronectin and collagen, lysyl oxidase (LOX) activity, interleukin-8 and activation of Rho signaling were analyzed in lung samples and pulmonary EC grown on soft (1.5 or 2.8 kPa) and stiff (40 kPa) substrates. LPS induced EC inflammatory activation accompanied by expression of ECM proteins, increase in LOX activity, and activation of Rho signaling. These effects were augmented in EC grown on stiff substrate. Stiffness-dependent enhancement of inflammation was associated with increased expression of Rho activator, GEF-H1. Inhibition of ECM crosslinking and stiffening by LOX suppression reduced EC inflammatory activation and GEF-H1 expression in response to LPS. In vivo, LOX inhibition attenuated LPS-induced expression of GEF-H1 and lung dysfunction. These findings present a novel mechanism of stiffness-dependent exacerbation of vascular inflammation and escalation of ALI via stimulation of GEF-H1-Rho pathway. This pathway represents a fundamental mechanism of positive feedback regulation of inflammation.
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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.