scholarly journals Extracellular Vesicles in Airway Homeostasis and Pathophysiology

2021 ◽  
Vol 11 (21) ◽  
pp. 9933
Author(s):  
Alberto Fucarino ◽  
Alessandro Pitruzzella ◽  
Stefano Burgio ◽  
Maria Concetta Zarcone ◽  
Domenico Michele Modica ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Extracellular Vesicles ◽  
Cell Types ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Innermost Layer ◽  
Different Cell Types

The epithelial–mesenchymal trophic unit (EMTU) is a morphofunctional entity involved in the maintenance of the homeostasis of airways as well as in the pathogenesis of several diseases, including asthma and chronic obstructive pulmonary disease (COPD). The “muco-microbiotic layer” (MML) is the innermost layer of airways made by microbiota elements (bacteria, viruses, archaea and fungi) and the surrounding mucous matrix. The MML homeostasis is also crucial for maintaining the healthy status of organs and its alteration is at the basis of airway disorders. Nanovesicles produced by EMTU and MML elements are probably the most important tool of communication among the different cell types, including inflammatory ones. How nanovesicles produced by EMTU and MML may affect the airway integrity, leading to the onset of asthma and COPD, as well as their putative use in therapy will be discussed here.

scholarly journals Differential expression of C-Reactive protein and Serum amyloid A in different cell types in the lung tissue of chronic obstructive pulmonary disease patients

2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Carmen Calero ◽  
Elena Arellano ◽  
Jose Luis Lopez-Villalobos ◽  
Verónica Sánchez-López ◽  
Nicolás Moreno-Mata ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Serum Amyloid A ◽  
Cell Types ◽  
Chronic Obstructive ◽  
C Reactive Protein ◽  
Obstructive Pulmonary Disease ◽  
Reactive Protein ◽  
Amyloid A ◽  
Different Cell Types

Surface Proteome of Plasma Extracellular Vesicles as Biomarkers for Pneumonia and Acute Exacerbation of Chronic Obstructive Pulmonary Disease

2019 ◽  
Author(s):  
Anna Lena Jung ◽  
Malene Møller Jørgensen ◽  
Rikke Bæk ◽  
Kathrin Griss ◽  
Maria Han ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Differential Diagnosis ◽  
Pulmonary Disease ◽  
Acute Exacerbation ◽  
Extracellular Vesicles ◽  
Cytotoxic T Lymphocyte ◽  
Area Under The Curve ◽  
Chronic Obstructive ◽  
Healthy Controls ◽  
Obstructive Pulmonary Disease

Abstract Background Community-acquired pneumonia (CAP) and acute exacerbation of chronic obstructive pulmonary disease (AECOPD) represent a major burden of disease and death and their differential diagnosis is critical. A potential source of relevant accessible biomarkers are blood-borne small extracellular vesicles (sEVs). Methods We performed an extracellular vesicle array to find proteins on plasma sEVs that are differentially expressed and possibly allow the differential diagnosis between CAP and AECOPD. Plasma samples were analyzed from 21 healthy controls, 24 patients with CAP, and 10 with AECOPD . The array contained 40 antibodies to capture sEVs, which were then visualized with a cocktail of biotin-conjugated CD9, CD63, and CD81 antibodies. Results We detected significant differences in the protein decoration of sEVs between healthy controls and patients with CAP or AECOPD. We found CD45 and CD28 to be the best discrimination markers between CAP and AECOPD in receiver operating characteristic analyses, with an area under the curve >0.92. Additional ensemble feature selection revealed the possibility to distinguish between CAP and AECOPD even if the patient with CAP had COPD, with a panel of CD45, CD28, CTLA4 (cytotoxic T-lymphocyte-associated protein 4), tumor necrosis factor–R-II, and CD16. Conclusion The discrimination of sEV-associated proteins is a minimally invasive method with potential to discriminate between CAP and AECOPD.

scholarly journals Human Umbilical Cord Mesenchymal Stem Cell-Derived Extracellular Vesicles Ameliorate Airway Inflammation in a Rat Model of chronic obstructive pulmonary disease (COPD)

2020 ◽  
Author(s):  
Noridzzaida Ridzuan ◽  
Norashikin Zakaria ◽  
Darius Widera ◽  
Jonathan Sheard ◽  
Mitsuru Morimoto ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Pulmonary Disease ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Rat Model ◽  
Chronic Obstructive ◽  
Human Umbilical Cord ◽  
Obstructive Pulmonary Disease

Abstract Background: Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin.Methods: In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSCs) derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSCs-derived EVs. Lung tissue was subjected to histological analysis using hematoxylin and eosin staining, alcian blue-periodic acid Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t-test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median±standard deviation (SD).Results: Both, transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, as well as a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions: In conclusion, we show that hUC-MSCs-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free based therapy for the treatment of COPD.

scholarly journals Muscarinic Receptors and Their Antagonists in COPD: Anti-Inflammatory and Antiremodeling Effects

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
George Karakiulakis ◽  
Michael Roth
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Extracellular Matrix ◽  
Pulmonary Disease ◽  
Muscarinic Receptors ◽  
Cell Types ◽  
Matrix Metalloproteases ◽  
Chronic Obstructive ◽  
Small Airways ◽  
Obstructive Pulmonary Disease ◽  
Anti Inflammatory

Muscarinic receptors are expressed by most cell types and mediate cellular signaling of their natural ligand acetylcholine. Thereby, they control numerous central and peripheral physiological organ responses to neuronal activity. In the human lung, muscarinic receptors are predominantly expressed by smooth muscle cells, epithelial cells, and fibroblasts. Antimuscarinic agents are used for the treatment of chronic obstructive pulmonary disease and to a lesser extent for asthma. They are primarily used as bronchodilators, but it is now accepted that they are also associated with anti-inflammatory, antiproliferative, and antiremodeling effects. Remodeling of the small airways is a major pathology in COPD and impairs lung function through changes of the extracellular matrix. Glycosaminoglycans, particularly hyaluronic acid, and matrix metalloproteases are among extracellular matrix molecules that have been associated with tissue inflammation and remodeling in lung diseases, including chronic obstructive pulmonary disease and asthma. Since muscarinic receptors have been shown to influence the homeostasis of glycosaminoglycans and matrix metalloproteases, these molecules may be proved valuable endpoint targets in clinical studies for the pharmacological exploitation of the anti-inflammatory and antiremodeling effects of muscarinic inhibitors in the treatment of chronic obstructive pulmonary disease and asthma.

scholarly journals Human umbilical cord mesenchymal stem cell-derived extracellular vesicles ameliorate airway inflammation in a rat model of chronic obstructive pulmonary disease (COPD)

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Noridzzaida Ridzuan ◽  
Norashikin Zakaria ◽  
Darius Widera ◽  
Jonathan Sheard ◽  
Mitsuru Morimoto ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Pulmonary Disease ◽  
Umbilical Cord ◽  
Extracellular Vesicles ◽  
Rat Model ◽  
Chronic Obstructive ◽  
Human Umbilical Cord ◽  
Obstructive Pulmonary Disease

Abstract Background Chronic obstructive pulmonary disease (COPD) is an incurable and debilitating chronic disease characterized by progressive airflow limitation associated with abnormal levels of tissue inflammation. Therefore, stem cell-based approaches to tackle the condition are currently a focus of regenerative therapies for COPD. Extracellular vesicles (EVs) released by all cell types are crucially involved in paracrine, extracellular communication. Recent advances in the field suggest that stem cell-derived EVs possess a therapeutic potential which is comparable to the cells of their origin. Methods In this study, we assessed the potential anti-inflammatory effects of human umbilical cord mesenchymal stem cell (hUC-MSC)-derived EVs in a rat model of COPD. EVs were isolated from hUC-MSCs and characterized by the transmission electron microscope, western blotting, and nanoparticle tracking analysis. As a model of COPD, male Sprague-Dawley rats were exposed to cigarette smoke for up to 12 weeks, followed by transplantation of hUC-MSCs or application of hUC-MSC-derived EVs. Lung tissue was subjected to histological analysis using haematoxylin and eosin staining, Alcian blue-periodic acid-Schiff (AB-PAS) staining, and immunofluorescence staining. Gene expression in the lung tissue was assessed using microarray analysis. Statistical analyses were performed using GraphPad Prism 7 version 7.0 (GraphPad Software, USA). Student’s t test was used to compare between 2 groups. Comparison among more than 2 groups was done using one-way analysis of variance (ANOVA). Data presented as median ± standard deviation (SD). Results Both transplantation of hUC-MSCs and application of EVs resulted in a reduction of peribronchial and perivascular inflammation, alveolar septal thickening associated with mononuclear inflammation, and a decreased number of goblet cells. Moreover, hUC-MSCs and EVs ameliorated the loss of alveolar septa in the emphysematous lung of COPD rats and reduced the levels of NF-κB subunit p65 in the tissue. Subsequent microarray analysis revealed that both hUC-MSCs and EVs significantly regulate multiple pathways known to be associated with COPD. Conclusions In conclusion, we show that hUC-MSC-derived EVs effectively ameliorate by COPD-induced inflammation. Thus, EVs could serve as a new cell-free-based therapy for the treatment of COPD.

scholarly journals Expression Analysis of Muscle-Specific miRNAs in Plasma-Derived Extracellular Vesicles from Patients with Chronic Obstructive Pulmonary Disease

Diagnostics ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 502
Author(s):  
Sara Carpi ◽  
Beatrice Polini ◽  
Dario Nieri ◽  
Nevio Dubbini ◽  
Alessandro Celi ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Receiver Operating Characteristic ◽  
Pulmonary Disease ◽  
Extracellular Vesicles ◽  
Operating Characteristic ◽  
Expression Profiles ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Group B

MicroRNAs (miRNAs) are a class of short non-coding RNAs involved in the regulation of gene expression and the control of several cellular processes at physiological and pathological levels. Furthermore, extracellular vesicles (EV), which are small membrane-bound vesicles secreted by cells in the extracellular environment, contain functional miRNAs. The remarkable deregulation of many miRNAs has been demonstrated in respiratory diseases. Among them, miR-206, miR-133a-5p, and miR-133a-3p are striated muscle-specific miRNAs (myo-miRNA), related to skeletal muscle dysfunction, one of the commonest systemic manifestations in patients with chronic obstructive pulmonary disease (COPD). Nevertheless, their circulating expression in COPD patients is not demonstrated. For these reasons, we performed a pilot study to analyze the expression profiles of myo-miRNAs in plasma-derived EV from patients with COPD. We analyzed the expression profiles of selected myo-miRNAs in plasma-derived EV from COPD. Receiver operating characteristic analyses were carried out to evaluate whether selected plasma miRNAs were able to discriminate between different groups of COPD patients. We found EV-embedded myo-miRNAs in the bloodstream of COPD patients. Specifically, miR-206, miR-133a-5p and miR-133a-3p were significantly upregulated in group B patients. Receiver operating characteristic analyses of the combination of these selected miRNAs showed their high capacity to discriminate group B from other COPD patients. Our data provide evidence that myo-miRNA are present in EV in the plasma of COPD patients and their expression (miR-206, miR-133a-5p, and miR-133a-3p) can discriminate group B from group C patients. The future analysis of a larger number of patients should allow us to obtain more refined correlations.

scholarly journals Single-cell transcriptomics reveal cell type-specific molecular changes and altered intercellular communications in chronic obstructive pulmonary disease

2021 ◽  
Author(s):  
Qiqing Huang ◽  
Jingshen Wang ◽  
Shaoran Shen ◽  
Yuanyuan Wang ◽  
Yan Chen ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Single Cell ◽  
Pulmonary Disease ◽  
Alveolar Epithelium ◽  
Cell Types ◽  
Chronic Obstructive ◽  
Cell Type ◽  
Obstructive Pulmonary Disease ◽  
Cell Type Specific ◽  
Intercellular Communications

AbstractChronic obstructive pulmonary disease (COPD) is a common and heterogeneous respiratory disease, the molecular complexity of which remains poorly understood, as well as the mechanisms by which aging and smoking facilitate COPD development. Here, using single-cell RNA sequencing of more than 65,000 cells from COPD and age-stratified control lung tissues of donors with different smoking histories, we identified monocytes, club cells, and macrophages as the most disease-, aging-, and smoking-relevant cell types, respectively. Notably, we found these highly cell-type specific changes under different conditions converged on cellular dysfunction of the alveolar epithelium. Deeper investigations revealed that the alveolar epithelium damage could be attributed to the abnormally activated monocytes in COPD lungs, which could be amplified via exhaustion of club cell stemness as ages. Moreover, the enhanced intercellular communications in COPD lungs as well as the pro-inflammatory interaction between macrophages and endothelial cells indued by smoking could facilitate signaling between monocyte and the alveolar epithelium. Our findings complement the existing model of COPD pathogenesis by emphasizing the contributions of the previously less appreciated cell types, highlighting their candidacy as potential therapeutic targets for COPD.

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