scholarly journals Distinct Exosomal miRNA Profiles from BALF and Lung Tissue from COPD and IPF Patients

2021 ◽  
Author(s):  
Gagandeep Kaur ◽  
Krishna Maremanda ◽  
Michael Campos ◽  
Hitendra Singh Chand ◽  
Feng Li ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Cell Communication ◽  
Differentially Expressed ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Copd Patients ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas ◽  
Exosomal Mirna

Background: Chronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic, progressive lung ailments which are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Exosomes are small extracellular vesicles attributed to carry proteins, mRNA, miRNA and sncRNA to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF in independent cohorts. Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were approximately 89.85 nm in size and ~2.95 X 1010 particles/mL. Lung-derived exosomes were ~146.04 nm in size and ~2.38 X 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls. Conclusions: Overall, we identified specific miRNAs to develop as biomarkers or targets for pathogenesis of these chronic lung diseases.

scholarly journals Distinct exosomal miRNA profiles from BALF and lung tissue from COPD and IPF patients

2021 ◽  
Author(s):  
Gagandeep Kaur ◽  
Krishna P Maremanda ◽  
Michael Campos ◽  
Hitendra S Chand ◽  
Feng Li ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Cell Communication ◽  
Differentially Expressed ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Copd Patients ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas ◽  
Exosomal Mirna

AbstractBackgroundChronic Obstructive Pulmonary Disease (COPD) and Idiopathic Pulmonary Fibrosis (IPF) are chronic, progressive lung ailments which are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Exosomes are small extracellular vesicles attributed to carry proteins, mRNA, miRNA and sncRNA to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of BALF or the lung tissue derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF and lung tissue-derived exosomes from healthy non-smokers, healthy smokers, and patients with COPD and IPF in independent cohorts.ResultsExosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were approximately 89.85 nm in size and ∼2.95 × 1010 particles/mL. Lung-derived exosomes were ∼146.04 nm in size and ∼2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, three- and five-fold downregulation of miR-122-5p amongst the lung tissue-derived exosomes from COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were key 55 differentially expressed miRNAs in the lung tissue-derived exosomes of IPF patients compared to non-smoking controls.ConclusionsOverall, we identified specific miRNAs to develop as biomarkers or targets for pathogenesis of these chronic lung diseases.

scholarly journals Distinct Exosomal miRNA Profiles from BALF and Lung Tissue of COPD and IPF Patients

2021 ◽  
Vol 22 (21) ◽  
pp. 11830
Author(s):  
Gagandeep Kaur ◽  
Krishna Prahlad Maremanda ◽  
Michael Campos ◽  
Hitendra S. Chand ◽  
Feng Li ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Cell Communication ◽  
Lavage Fluid ◽  
Differentially Expressed ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Rna Molecules ◽  
Chronic Lung Diseases ◽  
Copd Patients ◽  
Differentially Expressed Mirnas

Chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) are chronic, progressive lung ailments that are characterized by distinct pathologies. Early detection biomarkers and disease mechanisms for these debilitating diseases are lacking. Extracellular vesicles (EVs), including exosomes, are small, lipid-bound vesicles attributed to carry proteins, lipids, and RNA molecules to facilitate cell-to-cell communication under normal and diseased conditions. Exosomal miRNAs have been studied in relation to many diseases. However, there is little to no knowledge regarding the miRNA population of bronchoalveolar lavage fluid (BALF) or the lung-tissue-derived exosomes in COPD and IPF. Here, we determined and compared the miRNA profiles of BALF- and lung-tissue-derived exosomes of healthy non-smokers, smokers, and patients with COPD or IPF in independent cohorts. Results: Exosome characterization using NanoSight particle tracking and TEM demonstrated that the BALF-derived exosomes were ~89.85 nm in size with a yield of ~2.95 × 1010 particles/mL in concentration. Lung-derived exosomes were larger in size (~146.04 nm) with a higher yield of ~2.38 × 1011 particles/mL. NGS results identified three differentially expressed miRNAs in the BALF, while there was one in the lung-derived exosomes from COPD patients as compared to healthy non-smokers. Of these, miR-122-5p was three- or five-fold downregulated among the lung-tissue-derived exosomes of COPD patients as compared to healthy non-smokers and smokers, respectively. Interestingly, there were a large number (55) of differentially expressed miRNAs in the lung-tissue-derived exosomes of IPF patients compared to non-smoking controls. Conclusions: Overall, we identified lung-specific miRNAs associated with chronic lung diseases that can serve as potential biomarkers or therapeutic targets.

scholarly journals The roles of exosomal miRNAs and lncRNAs in lung diseases

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Yang Li ◽  
Zhengrong Yin ◽  
Jinshuo Fan ◽  
Siyu Zhang ◽  
Weibing Yang
Keyword(s):  
Lung Cancer ◽  
Information Exchange ◽  
Lung Diseases ◽  
Cell Communication ◽  
Diagnostic Methods ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Diagnostic Biomarkers ◽  
Exosomal Mirnas ◽  
New Ideas

Abstract An increasing number of studies have reported that exosomes released from various cells can serve as mediators of information exchange between different cells. With further exploration of exosome content, a more accurate molecular mechanism involved in the process of cell-to-cell communication has been revealed; specifically, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are shuttled by exosomes. In addition, exosomal miRNAs and lncRNAs may play vital roles in the pathogenesis of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), lung cancer, and asthma. Consequently, exosomal miRNAs and lncRNAs show promise as diagnostic biomarkers and therapeutic targets in several lung diseases. This review will summarize recent knowledge about the roles of exosomal miRNAs and lncRNAs in lung diseases, which has shed light on the discovery of novel diagnostic methods and treatments for these disorders. Because there is almost no published literature about exosomal lncRNAs in COPD, asthma, interstitial lung disease, or tuberculosis, we summarize the roles of exosomal lncRNAs only in lung cancer in the second section. This may inspire some new ideas for researchers who are interested in whether lncRNAs shuttled by exosomes may play roles in other lung diseases.

scholarly journals Whole transcriptome analysis of human lung tissue to identify COPD-associated gene

2020 ◽  
Author(s):  
Qiuyu Li ◽  
Yizhang Zhu ◽  
Aiyuan Zhou ◽  
Yuxin Yin
Keyword(s):  
Lung Tissue ◽  
Human Lung ◽  
Tissue Expression ◽  
Chronic Obstructive ◽  
Human Lung Tissue ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Matrix Organization ◽  
Whole Transcriptome Analysis ◽  
Whole Transcriptome

Abstract Identification of the dysfunctional genes in human lung from patients with Chronic obstructive pulmonary disease (COPD) will help up to understand the pathology of this disease. Here, using transcriptomic data of lung tissue for 91 COPD cases and 182 matched healthy controls from the Genotype-Tissue Expression (GTEx) database. Employing a stringent model controlling for known covariates and hidden confounders, we identified 1,359 significant differentially expressed genes (DEG) with 707 upregulated and 602 downregulated respectively. We evaluated the identified DEGs in an independent microarray cohort of 219 COPD and 108 controls, demonstrating the robustness of our result. Functional annotation of COPD-associated genes highlighted the activation of complement cascade, dysregulation of inflammatory response and extracellular matrix organization in the COPD patients. In addition, we identified several novel key-hub genes involved in the COPD pathogenesis using a network analysis method. In summary, our study represents the comprehensive analysis of gene expression on COPD with the largest sample size providing great resource for the molecular research in the COPD community.

scholarly journals Increased pulmonary serotonin transporter in patients with chronic obstructive pulmonary disease who developed pulmonary hypertension

2020 ◽  
Author(s):  
Armin Frille ◽  
Michael Rullmann ◽  
Georg-Alexander Becker ◽  
Marianne Patt ◽  
Julia Luthardt ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Hypertension ◽  
Pulmonary Disease ◽  
Serotonin Transporter ◽  
Lung Tissue ◽  
Chronic Obstructive ◽  
Right Heart ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Pet Ct

Abstract Purpose Pulmonary hypertension (PH) is characterized by a progressive remodelling of the pulmonary vasculature resulting in right heart failure and eventually death. The serotonin transporter (SERT) may be involved in the pathogenesis of PH in patients with chronic-obstructive pulmonary disease (COPD). This study investigated for the first time the SERT in vivo availability in the lungs of patients with COPD and PH (COPD+PH). Methods SERT availability was assessed using SERT-selective [11C]DASB and positron emission tomography/computed tomography (PET/CT) with dynamic acquisition over 30 min in 4 groups of 5 participants each: COPD, COPD+PH, pulmonary arterial hypertension, and a healthy control (HC). Time activity curves were generated based on a volume of interest within the middle lobe. Tissue-to-blood concentration ratios after 25 to 30 min (TTBR25–30) served as receptor parameter for group comparison and were corrected for lung tissue attenuation. Participants underwent comprehensive pulmonary workup. Statistical analysis included group comparisons and correlation analysis. Results [11C]DASB uptake peak values did not differ among the cohorts after adjusting for lung tissue attenuation, suggesting equal radiotracer delivery. Both the COPD and COPD+PH cohort showed significantly lower TTBR25–30 values after correction for lung attenuation than HC. Attenuation corrected TTBR25–30 values were significantly higher in the COPD+PH cohort than those in the COPD cohort and higher in non-smokers than in smokers. They positively correlated with invasively measured severity of PH and inversely with airflow limitation and emphysema. Considering all COPD patients ± PH, they positively correlated with right heart strain (NT-proBNP). Conclusion By applying [11C]DASB and PET/CT, semiquantitative measures of SERT availability are demonstrated in the lung vasculature of patients with COPD and/or PH. COPD patients who developed PH show increased pulmonary [11C]DASB uptake compared to COPD patients without PH indicating an implication of pulmonary SERT in the development of PH in COPD patients.

scholarly journals Serum-Derived Neuronal Exosomal miRNAs as Biomarkers of Acute Severe Stress

2021 ◽  
Vol 22 (18) ◽  
pp. 9960
Author(s):  
Minkyoung Sung ◽  
Soo-Eun Sung ◽  
Kyung-Ku Kang ◽  
Joo-Hee Choi ◽  
Sijoon Lee ◽  
...  
Keyword(s):  
Acute Stress ◽  
Stress Hormones ◽  
Differentially Expressed ◽  
Control Group ◽  
Severe Stress ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Exosomal Mirnas ◽  
Differentially Expressed Mirnas ◽  
Exosomal Mirna

Stress is the physical and psychological tension felt by an individual while adapting to difficult situations. Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed to determine whether differentially expressed miRNAs could be used as biomarkers of acute stress. Specifically, acute severe stress was induced in Sprague-Dawley rats via electric foot-shock treatment. In this acute severe-stress model, time-dependent changes in the expression levels of stress hormones and neuroinflammation-related markers were analyzed. In addition, nEVs were isolated from the serum of control mice and stressed mice at various time points to determine when brain damage was most prominent; this was found to be 7 days after foot shock. Next-generation sequencing was performed to compare neuronal exosomal miRNA at day 7 with the neuronal exosomal miRNA of the control group. From this analysis, 13 upregulated and 11 downregulated miRNAs were detected. These results show that specific miRNAs are differentially expressed in nEVs from an acute severe-stress animal model. Thus, this study provides novel insights into potential stress-related biomarkers.

scholarly journals Differential plasma exosomal long non-coding RNAs expression profiles and their emerging role in E-cigarette users, cigarette, waterpipe, and dual smokers

PLoS ONE ◽  
2020 ◽  
Vol 15 (12) ◽  
pp. e0243065 ◽  
Author(s):  
Gagandeep Kaur ◽  
Kameshwar Singh ◽  
Krishna P. Maremanda ◽  
Dongmei Li ◽  
Hitendra S. Chand ◽  
...  
Keyword(s):  
Expression Profiles ◽  
Transcriptional Profiling ◽  
Critical Role ◽  
Cell Communication ◽  
Chronic Obstructive ◽  
Biological Processes ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Non Coding Rnas ◽  
Differentiation And Proliferation

Long non-coding RNAs (lncRNAs) are the varied set of transcripts that play a critical role in biological processes like gene regulation, transcription, post-transcriptional modification, and chromatin remodeling. Recent studies have reported the presence of lncRNAs in the exosomes that are involved in regulating cell-to-cell communication in lung pathologies including lung cancer, chronic obstructive pulmonary disease (COPD), asthma, and idiopathic pulmonary fibrosis (IPF). In this study, we compared the lncRNA profiles in the plasma-derived exosomes amongst non-smokers (NS), cigarette smokers (CS), E-cig users (E-cig), waterpipe smokers (WP) and dual smokers (CSWP) using GeneChip™ WT Pico kit for transcriptional profiling. We found alterations in a distinct set of lncRNAs among subjects exposed to E-cig vapor, cigarette smoke, waterpipe smoke and dual smoke with some overlaps. Gene enrichment analyses of the differentially expressed lncRNAs demonstrated enrichment in the lncRNAs involved in crucial biological processes including steroid metabolism, cell differentiation and proliferation. Thus, the characterized lncRNA profiles of the plasma-derived exosomes from smokers, vapers, waterpipe users, and dual smokers will help identify the biomarkers relevant to chronic lung diseases such as COPD, asthma or IPF.

scholarly journals Prevalence of different comorbidities in chronic obstructive pulmonary disease among Shahrekord PERSIAN cohort study in southwest Iran

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Fatemeh Zeynab Kiani ◽  
Ali Ahmadi
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Health Care ◽  
Metabolic Syndrome ◽  
Cohort Study ◽  
Pulmonary Disease ◽  
Chronic Obstructive ◽  
Cross Sectional ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Copd Patients

AbstractComorbidities are common in chronic obstructive pulmonary disease (COPD) patients. This study was conducted to determine the prevalence of common comorbidities in patients with COPD compared with people without COPD. This cross-sectional, population-based study was performed on 6961 adults aged 35–70 years enrolled in the Shahrekord PERSIAN cohort study. Data (demographic and clinical characteristics, comorbidities, anthropometric and blood pressure measurements, laboratory, and spirometry tests) collection was performed according to the cohort protocol from 2015 to 2019. In the present study, 215 (3.1%) patients were diagnosed with COPD and 1753 (25.18%) ones with restrictive lung patterns. The mean age of COPD patients was 52.5 ± 9.76 years. 55.8% of patients were male, 17.7% were current smokers and 12.1% had a history of smoking or were former smokers. 5.6% of patients had no comorbidity and 94.5% had at least one comorbidity. The most common comorbidities in COPD patients were dyslipidemia (70.2%), hypertension (30.2%), metabolic syndrome (22.8%), and diabetes (16.7%). The most common comorbidities in individuals with a restrictive spirometry pattern were dyslipidemia (68.9%), metabolic syndrome (27.2%), hypertension (26.1%), depression (17.6%), and fatty liver (15.5%). The logistic regression analysis with 95% confidence interval (95%CI) of odds ratio (OR) showed that comorbidities of chronic lung diseases (OR = 2.12, 95% CI 1.30–3.44), diabetes (OR = 1.54, 95%CI 1.03–2.29), cardiovascular disease (OR = 1.52, 95%CI 1.17–2.43), and hypertension (OR = 1.4, 95%CI 1.02–1.99) were more likely to occur in COPD patients than in healthy individuals. Knowing these prevalence rates and related information provides new insights on comorbidities to reduce disease burden and develop preventive interventions and to regulate health care resources to meet the needs of patients in primary health care.

scholarly journals The Role of Extracellular Vesicles as a Shared Disease Mechanism Contributing to Multimorbidity in Patients With COPD

2021 ◽  
Vol 12 ◽  
Author(s):  
Laura V. Reid ◽  
C. Mirella Spalluto ◽  
Alastair Watson ◽  
Karl J. Staples ◽  
Tom M. A. Wilkinson
Keyword(s):  
Chronic Diseases ◽  
Extracellular Vesicles ◽  
Respiratory Infections ◽  
Biological Fluids ◽  
Recipient Cell ◽  
Cell Communication ◽  
Management Approach ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death worldwide. Individuals with COPD typically experience a progressive, debilitating decline in lung function as well as systemic manifestations of the disease. Multimorbidity, is common in COPD patients and increases the risk of hospitalisation and mortality. Central to the genesis of multimorbidity in COPD patients is a self-perpetuating, abnormal immune and inflammatory response driven by factors including ageing, pollutant inhalation (including smoking) and infection. As many patients with COPD have multiple concurrent chronic conditions, which require an integrative management approach, there is a need to greater understand the shared disease mechanisms contributing to multimorbidity. The intercellular transfer of extracellular vesicles (EVs) has recently been proposed as an important method of local and distal cell-to-cell communication mediating both homeostatic and pathological conditions. EVs have been identified in many biological fluids and provide a stable capsule for the transfer of cargo including proteins, lipids and nucleic acids. Of these cargo, microRNAs (miRNAs), which are short 17-24 nucleotide non-coding RNA molecules, have been amongst the most extensively studied. There is evidence to support that miRNA are selectively packaged into EVs and can regulate recipient cell gene expression including major pathways involved in inflammation, apoptosis and fibrosis. Furthermore changes in EV cargo including miRNA have been reported in many chronic diseases and in response to risk factors including respiratory infections, noxious stimuli and ageing. In this review, we discuss the potential of EVs and EV-associated miRNA to modulate shared pathological processes in chronic diseases. Further delineating these may lead to the identification of novel biomarkers and therapeutic targets for patients with COPD and multimorbidities.

scholarly journals The inflammasome pathway in stable COPD and acute exacerbations

2016 ◽  
Vol 2 (3) ◽  
pp. 00002-2016 ◽  
Author(s):  
Rosa Faner ◽  
Patricia Sobradillo ◽  
Aina Noguera ◽  
Cristina Gomez ◽  
Tamara Cruz ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Nlrp3 Inflammasome ◽  
Chronic Obstructive ◽  
Inflammasome Activation ◽  
Tissue Samples ◽  
Obstructive Pulmonary Disease ◽  
Clinical Recovery ◽  
Caspase 1 ◽  
Copd Patients ◽  
Never Smokers

Chronic obstructive pulmonary disease (COPD) is characterised by pulmonary and systemic inflammation that bursts during exacerbations of the disease (ECOPD). The NLRP3 inflammasome is a key regulatory molecule of the inflammatory response. Its role in COPD is unclear.We investigated the NLRP3 inflammasome status in: 1) lung tissue samples from 38 patients with stable COPD, 15 smokers with normal spirometry and 14 never-smokers; and 2) sputum and plasma samples from 56 ECOPD patients, of whom 41 could be reassessed at clinical recovery.We observed that: 1) in lung tissue samples of stable COPD patients, NLRP3 and interleukin (IL)-1β mRNA were upregulated, but both caspase-1 and ASC were mostly in inactive form, and 2) during infectious ECOPD, caspase-1, oligomeric ASC and associated cytokines (IL-1β, IL-18) were significantly increased in sputum compared with clinical recovery.The NLRP3 inflammasome is primed, but not activated, in the lungs of clinically stable COPD patients. Inflammasome activation occurs during infectious ECOPD. The results of this study suggest that the inflammasome participates in the inflammatory burst of infectious ECOPD.

Sign in / Sign up

Export Citation Format

Share Document