ArticleAmerican journal of physiology. Lung cellular and molecular physiology2012
Stimulation of Rho signaling by pathologic mechanical stretch is a "second hit" to Rho-independent lung injury induced by IL-6.
Article in American journal of physiology. Lung cellular and molecular physiology, 2012. 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, 66 citations in OpenAlex.
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- CMTM3 regulates vascular endothelial cell dysfunction by influencing pulmonary vascular endothelial permeability and inflammation in ARDS.Frontiers in immunology · 2025Article
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- COVID-19 and Oxidative Stress.Biochemistry. Biokhimiia · 2020Review
- Transient receptor potential canonical 1 channel mediates the mechanical stress‑induced epithelial‑mesenchymal transition of human bronchial epithelial (16HBE) cells.International journal of molecular medicine · 2020Article
- The RNFT2/IL-3Rα axis regulates IL-3 signaling and innate immunity.JCI insight · 2020Article
- Biomechanical Forces and Oxidative Stress: Implications for Pulmonary Vascular Disease.Antioxidants & redox signaling · 2019Review
- Molecular Mechanisms of Ventilator-Induced Lung Injury.Chinese medical journal · 2018Review
- Selective Role of Vinculin in Contractile Mechanisms of Endothelial Permeability.American journal of respiratory cell and molecular biology · 2016Article
- Using cultured endothelial cells to study endothelial barrier dysfunction: Challenges and opportunities.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Activation of Vascular Endothelial Growth Factor (VEGF) Receptor 2 Mediates Endothelial Permeability Caused by Cyclic Stretch.The Journal of biological chemistry · 2016Article
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- VE-cadherin involved in the pulmonary microvascular endothelial cell barrier injury induced by angiotensin II through modulating the cellular apoptosis and skeletal rearrangement.American journal of translational research · 2016Article
- Dephosphorylation of Y685-VE-Cadherin Involved in Pulmonary Microvascular Endothelial Barrier Injury Induced by Angiotensin II.Mediators of inflammation · 2016Article
- Coming to terms with tissue engineering and regenerative medicine in the lung.American journal of physiology. Lung cellular and molecular physiology · 2015Review
- The intracerebroventricular injection of rimonabant inhibits systemic lipopolysaccharide-induced lung inflammation.Journal of neuroimmunology · 2015Article
- Activation of EPBritish journal of pharmacology · 2015Article
- Alterations of lung microbiota in a mouse model of LPS-induced lung injury.American journal of physiology. Lung cellular and molecular physiology · 2015Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Most patients with acute lung injury (ALI) and acute respiratory distress syndrome of septic and nonseptic nature require assisted ventilation with positive pressure, which at suboptimal range may further exacerbate lung dysfunction. Previous studies described enhancement of agonist-induced Rho GTPase signaling and endothelial cell (EC) permeability in EC cultures exposed to pathologically relevant cyclic stretch (CS) magnitudes. This study examined a role of pathologic CS in modulation of pulmonary EC permeability caused by IL-6, a cytokine increased in sepsis and acting in a Rho-independent manner. IL-6 increased EC permeability, which was associated with activation of Jak/signal transducers and activators of transcription, p38 MAP kinase, and NF-κB signaling and was augmented by EC exposure to 18% CS. Rho kinase inhibitor Y-27632 suppressed the synergistic effect of 18% CS on IL-6-induced EC monolayer disruption but did not alter the IL-6 effects on static EC culture. 18% CS also increased IL-6-induced ICAM-1 expression by pulmonary EC and neutrophil adhesion, which was attenuated by Y-27632. Intratracheal IL-6 administration in C57BL/6J mice increased protein content and cell count in bronchoalveolar lavage fluid. These changes were augmented by high tidal volume mechanical ventilation (HTV; 30 ml/kg, 4 h). Intravenous injection of Y-27632 suppressed IL6/HTV-induced lung injury. In conclusion, this study proposes a novel mechanism contributing to two-hit model of ALI: in addition to synergistic effects on Rho-dependent endothelial hyper-permeability triggered by thrombin, TNFα, LPS, or other agonists, ventilator-induced lung injury-relevant CS may also exacerbate Rho-independent mechanisms of EC permeability induced by other inflammatory mediators such as IL-6 via mechanisms involving Rho activity.
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