scholarly journals Gap Junction Channel Modulates Pulmonary Vascular Permeability through Calcium in Acute Lung Injury: An Experimental Study

Respiration ◽  
2010 ◽  
Vol 80 (3) ◽  
pp. 236-245 ◽  
Author(s):  
Jinzhou Zhang ◽  
Wen Wang ◽  
Jing Sun ◽  
Qiang Li ◽  
Jincheng Liu ◽  
...  
Keyword(s):  
Experimental Study ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Gap Junction ◽  
Vascular Permeability ◽  
Pulmonary Vascular Permeability ◽  
Gap Junction Channel

Sodium houttuyfonate relieves acute lung injury by nano micellar carrier and inhibits mitogen-activated protein kinase and nuclear factor kappa-B activation in mice

2021 ◽  
Vol 11 (5) ◽  
pp. 781-788
Author(s):  
Kai Yang ◽  
Shushu Yan ◽  
Jian Xie ◽  
Fang Xie ◽  
Zhenzhen Zhao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Vascular Permeability ◽  
Delivery System ◽  
Lung Tissue ◽  
Good Effect ◽  
Pulmonary Vascular Permeability ◽  
Cytokine Levels ◽  
And Oxidative Stress

Acute lung injury (ALI) is characterized by increased pulmonary vascular permeability in response to the accumulation of inflammatory cells, release of inflammatory cytokines, and activated oxidative stress. The present study was performed to investigate the effect of sodium houttuyfonate (SH), an extract of Houttuynia cordata, on inflammatory response and oxidative stress in ALI induced by lipopolysaccharides (LPS). Male C57BL/6 mice were randomly allocated to control, LPS, dimethyl sulfoxide (DMSO), and SH groups. The ALI model was established by intratracheal LPS injection. Lung tissue was collected 6 h after LPS injection for histopathological analysis, measurement of wet-to-dry ratio, myeloperoxidase (MPO) and oxidative stress levels, and the p38, jun N-terminal kinase (JNK), extracellular regulated kinase (ERK), and p65 phosphorylation levels. Bronchoalveolar fluid (BALF) was collected for the detection of protein concentration, MPO and cytokine levels. The histopathological test showed that SH significantly alleviates damage to pulmonary tissue. Improved vascular permeability was indicated by reduced BALF protein level and lung wet-to-dry ratio in the SH group. MPO levels were decreased in lung tissue and BALF. Oxidative stress and inflammatory responses were inhibited by SH, as indicated by MDA, SOD and cytokine levels. The MAPK and NF-KB pathways were inhibited as shown by the attenuated phosphorylation of p38, JNK, ERK and p65. Sodium houttuyfonate exhibited a protective role against LPS-induced lung injury through anti-oxidative and anti-inflammatory effects. The MAPK and NF-K B pathways may be inhibited by sodium houttuyfonate. Sodium Houttuynin has a good effect on a variety of acute infectious diseases, but its solubility and stability are insufficient, which limits its efficacy. Nano delivery system can enhance the effective ingredients of traditional Chinese medicine, reduce the toxic and side effects of drugs, and improve their medicinal properties. Therefore, this paper adopts nano delivery system to assist drug use and improve research efficiency.

Cytoskeletal regulation of pulmonary vascular permeability

2001 ◽  
Vol 91 (4) ◽  
pp. 1487-1500 ◽  
Author(s):  
Steven M. Dudek ◽  
Joe G. N. Garcia
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Actin Cytoskeleton ◽  
Vascular Permeability ◽  
Barrier Function ◽  
Focal Adhesions ◽  
Pulmonary Vasculature ◽  
High Morbidity ◽  
Pulmonary Vascular Permeability ◽  
Cell Matrix

The endothelial cell (EC) lining of the pulmonary vasculature forms a semipermeable barrier between the blood and the interstitium of the lung. Disruption of this barrier occurs during inflammatory disease states such as acute lung injury and acute respiratory distress syndrome and results in the movement of fluid and macromolecules into the interstitium and pulmonary air spaces. These processes significantly contribute to the high morbidity and mortality of patients afflicted with acute lung injury. The critical importance of pulmonary vascular barrier function is shown by the balance between competing EC contractile forces, which generate centripetal tension, and adhesive cell-cell and cell-matrix tethering forces, which regulate cell shape. Both competing forces in this model are intimately linked through the endothelial cytoskeleton, a complex network of actin microfilaments, microtubules, and intermediate filaments, which combine to regulate shape change and transduce signals within and between EC. A key EC contractile event in several models of agonist-induced barrier dysfunction is the phosphorylation of regulatory myosin light chains catalyzed by Ca2+/calmodulin-dependent myosin light chain kinase and/or through the activity of the Rho/Rho kinase pathway. Intercellular contacts along the endothelial monolayer consist primarily of two types of complexes (adherens junctions and tight junctions), which link to the actin cytoskeleton to provide both mechanical stability and transduction of extracellular signals into the cell. Focal adhesions provide additional adhesive forces in barrier regulation by forming a critical bridge for bidirectional signal transduction between the actin cytoskeleton and the cell-matrix interface. Increasingly, the effects of mechanical forces such as shear stress and ventilator-induced stretch on EC barrier function are being recognized. The critical role of the endothelial cytoskeleton in integrating these multiple aspects of pulmonary vascular permeability provides a fertile area for the development of clinically important barrier-modulating therapies.

scholarly journals BMSC-Derived Exosomes Ameliorate LPS-Induced Acute Lung Injury by miR-384-5p-Controlled Alveolar Macrophage Autophagy

2021 ◽  
Vol 2021 ◽  
pp. 1-23
Author(s):  
Xuan Liu ◽  
Chengjin Gao ◽  
Yang Wang ◽  
Lei Niu ◽  
Shaowei Jiang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Alveolar Macrophage ◽  
Vascular Permeability ◽  
Alveolar Macrophages ◽  
Weight Ratio ◽  
Beclin 1 ◽  
Cell Counting ◽  
Pulmonary Vascular Permeability ◽  
Therapeutic Mechanism

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are common critical diseases. Bone marrow mesenchymal stem cell (BMSC) transplantation is previously shown to effectively rescue injured lung tissues. The therapeutic mechanism of BMSC-derived exosomes is not fully understood. Here, we investigated the BMSC-derived exosomal microRNAs (miRNAs) on effecting lipopolysaccharide- (LPS-) induced ALI and its mechanism. In vitro, rat alveolar macrophages were treated with or without exosomes in the presence of 10 μg/ml LPS for 24 h. Cell viability was determined with Cell Counting Kit-8 assay. Apoptotic ratio was determined with TUNEL and Annexin V-FITC/PI double staining. The levels of miR-384-5p and autophagy-associated genes were measured by RT-qPCR and western blot. Autophagy was observed by TEM and assessed by means of the mRFP-GFP-LC3 adenovirus transfection assay. In vivo, we constructed LPS-induced ALI rat models. Exosomes were injected into rats via the caudal vein or trachea 4 h later after LPS treatment. The lung histological pathology was determined by H&E staining. Pulmonary vascular permeability was assessed by wet-to-dry weight ratio and Evans blue dye leakage assay, and inflammatory cytokines in serum and BALF were measured by ELISA. Furthermore, the therapeutic mechanism involved in miR-384-5p and Beclin-1 was determined. The results showed that BMSC-derived exosomes were taken up by the alveolar macrophages and attenuated LPS-induced alveolar macrophage viability loss and apoptosis. Exosomes effectively improved the survival rate of ALI rats within 7 days, which was associated with alleviating lung pathological changes and pulmonary vascular permeability and attenuating inflammatory response. Furthermore, this study for the first time found that miR-384-5p was enriched in BMSC-derived exosomes, and exosomal miR-384-5p resulted in relieving LPS-injured autophagy disorder in alveolar macrophages by targeting Beclin-1. Therefore, exosomal miR-384-5p could be demonstrated as a promising therapeutic strategy for ALI/ARDS.

Vascular endothelial growth factor and related molecules in acute lung injury

2004 ◽  
Vol 97 (5) ◽  
pp. 1605-1617 ◽  
Author(s):  
Marco Mura ◽  
Claudia C. dos Santos ◽  
Duncan Stewart ◽  
Mingyao Liu
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Vascular Permeability ◽  
Animal Experiments ◽  
Disease Process ◽  
Pulmonary Vascular Permeability ◽  
Capillary Membrane ◽  
Organ Systems ◽  
And Function

VEGFs and their receptors have been implicated in the regulation of vascular permeability in many organ systems, including the lung. Increased permeability and interstitial and pulmonary edema are prominent features of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Extrapolating data from other organ systems and animal experiments have suggested that overexpression of VEGF functions primarily as proinjurious molecules in the lung. Recent data, from animal models as well as from patients with ARDS, have shown decreased levels of VEGF in the lung. The role of VEGF and related molecules in ALI/ARDS is, therefore, controversial: what has become clear is that there are many unique features in the regulation of pulmonary vascular permeability and in VEGF expression in the lung. In this review, we explore a growing body of literature looking at the expression and function of VEGF and related molecules in different models of ALI and in patients with ALI/ARDS. Novel evidence points to a potential role of VEGF in promoting repair of the alveolar-capillary membrane during recovery from ALI/ARDS. Understanding the role of VEGF in this disease process is crucial for developing new therapeutic strategies for ALI/ARDS.

scholarly journals Protectin conjugates in tissue regeneration 1 restores lipopolysaccharide-induced pulmonary endothelial glycocalyx loss via ALX/SIRT1/NF-kappa B axis

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Xin-Yang Wang ◽  
Xin-Yu Li ◽  
Cheng-Hua Wu ◽  
Yu Hao ◽  
Pan-Han Fu ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Inflammatory Cytokines ◽  
Tissue Regeneration ◽  
Umbilical Vein ◽  
Endothelial Glycocalyx ◽  
Lipid Mediator ◽  
Protective Effects ◽  
Pulmonary Vascular Permeability

Abstract Background Endothelial glycocalyx loss is integral to increased pulmonary vascular permeability in sepsis-related acute lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is a novel macrophage-derived lipid mediator exhibiting potential anti-inflammatory and pro-resolving benefits. Methods PCTR1 was administrated intraperitoneally with 100 ng/mouse after lipopolysaccharide (LPS) challenged. Survival rate and lung function were used to evaluate the protective effects of PCTR1. Lung inflammation response was observed by morphology and inflammatory cytokines level. Endothelial glycocalyx and its related key enzymes were measured by immunofluorescence, ELISA, and Western blot. Afterward, related-pathways inhibitors were used to identify the mechanism of endothelial glycocalyx response to PCTR1 in mice and human umbilical vein endothelial cells (HUVECs) after LPS administration. Results In vivo, we show that PCTR1 protects mice against lipopolysaccharide (LPS)-induced sepsis, as shown by enhanced the survival and pulmonary function, decreased the inflammatory response in lungs and peripheral levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-6, and interleukin-1β. Moreover, PCTR1 restored lung vascular glycocalyx and reduced serum heparin sulphate (HS), syndecan-1 (SDC-1), and hyaluronic acid (HA) levels. Furthermore, we found that PCTR1 downregulated heparanase (HPA) expression to inhibit glycocalyx degradation and upregulated exostosin-1 (EXT-1) protein expression to promote glycocalyx reconstitution. Besides, we observed that BAY11-7082 blocked glycocalyx loss induced by LPS in vivo and in vitro, and BOC-2 (ALX antagonist) or EX527 (SIRT1 inhibitor) abolished the restoration of HS in response to PCTR1. Conclusion PCTR1 protects endothelial glycocalyx via ALX receptor by regulating SIRT1/NF-κB pathway, suggesting PCTR1 may be a significant therapeutic target for sepsis-related acute lung injury.

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