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 Whole transcriptome analyis of human lung tissue to identify COPD-associated gene

2020 ◽  
Author(s):  
Yizhang Zhu ◽  
Qiuyu Li ◽  
Aiyuan Zhou ◽  
Alexandra C. Racanelli ◽  
Augustine M.K. Choi ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Lung Tissue ◽  
Human Lung ◽  
R Package ◽  
Tissue Expression ◽  
Chronic Obstructive ◽  
Common Disease ◽  
Human Lung Tissue ◽  
Obstructive Pulmonary Disease

Abstract Background: Chronic obstructive pulmonary disease (COPD) is a common disease characterized by persistent respiratory symptoms and airflow restriction. The mechanisms underlying pathogenesis in COPD are still poorly understood. 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. To identify the dysfunctional genes in human lung from patients with Chronic obstructive pulmonary disease (COPD). We used transcriptomic data of lung tissue for 91 COPD cases and 182 matched healthy controls from the Genotype-Tissue Expression (GTEx) database. We employed a stringent model controlling for known covariates and hidden confounders. DESeq2 R package (v1.20.0) was used to test for differential expression.Results: 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.Conclusion: 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 Identification of novel target genes in human lung tissue involved in chronic obstructive pulmonary disease

2018 ◽  
Vol Volume 13 ◽  
pp. 2255-2259 ◽  
Author(s):  
Lena Heinbockel ◽  
Sebastian Marwitz ◽  
Andra Schromm ◽  
Henrik Watz ◽  
Christian Kugler ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Lung Tissue ◽  
Target Genes ◽  
Human Lung ◽  
Chronic Obstructive ◽  
Human Lung Tissue ◽  
Obstructive Pulmonary Disease ◽  
Novel Target

Proteomics of Human Lung Tissue Identifies Surfactant Protein A as a Marker of Chronic Obstructive Pulmonary Disease

2008 ◽  
Vol 7 (12) ◽  
pp. 5125-5132 ◽  
Author(s):  
Steffen Ohlmeier ◽  
Minna Vuolanto ◽  
Tuula Toljamo ◽  
Katri Vuopala ◽  
Kaisa Salmenkivi ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Lung Tissue ◽  
Human Lung ◽  
Protein A ◽  
Surfactant Protein ◽  
Surfactant Protein A ◽  
Chronic Obstructive ◽  
Human Lung Tissue ◽  
Obstructive Pulmonary Disease

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 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 Cell-Specific Transcriptome of the COPD Alveolar Niche

2021 ◽  
Author(s):  
Maor Sauler ◽  
John McDonough ◽  
Taylor Adams ◽  
Neeharika Kotahpalli ◽  
Jonas Schupp ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Human Lung Tissue ◽  
Tissue Samples ◽  
Obstructive Pulmonary Disease ◽  
Alveolar Epithelial ◽  
Network Analyses ◽  
Capillary Endothelial Cells ◽  
Chemokine Signalling

Abstract Chronic Obstructive Pulmonary Disease (COPD) is a leading cause of death worldwide. To identify cell-specific mechanisms underlying COPD pathobiology, we analysed single-cell RNA sequencing (scRNAseq) profiles of explanted lung tissue from subjects with advanced COPD or control lungs. Findings were validated with scRNAseq of lungs from mice exposed to 10 months of cigarette smoke (CS), isolated human alveolar epithelial cells, and immunostaining of human lung tissue samples. We identified a subpopulation of alveolar epithelial type II cells with transcriptional evidence for aberrant cellular metabolism and reduced cellular stress tolerance, exemplified by decreased expression of the stress-response gene NUPR1. Network analyses identified an important role for inflamed capillary endothelial cells in COPD, particularly through CXCL-motif chemokine signalling. Finally, we detected a metallothionein expressing macrophage subpopulation unique to COPD. Collectively, these findings highlight cell-specific mechanisms involved in the pathobiology of advanced COPD.

scholarly journals Whole transcriptome analyis of human lung tissue to identify COPD-associated genes

Genomics ◽  
2020 ◽  
Vol 112 (5) ◽  
pp. 3135-3141
Author(s):  
Yizhang Zhu ◽  
Aiyuan Zhou ◽  
Qiuyu Li
Keyword(s):  
Lung Tissue ◽  
Human Lung ◽  
Human Lung Tissue ◽  
Whole Transcriptome

scholarly journals Human lung extracellular matrix hydrogels resemble the stiffness and viscoelasticity of native lung tissue

2020 ◽  
Vol 318 (4) ◽  
pp. L698-L704 ◽  
Author(s):  
R. H. J. de Hilster ◽  
P. K. Sharma ◽  
M. R. Jonker ◽  
E. S. White ◽  
E. A. Gercama ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Lung Tissue ◽  
Viscoelastic Properties ◽  
Human Lung ◽  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Human Lung Tissue ◽  
Native Tissue ◽  
Maxwell Element ◽  
Chronic Lung Diseases

Chronic lung diseases such as idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) are associated with changes in extracellular matrix (ECM) composition and abundance affecting the mechanical properties of the lung. This study aimed to generate ECM hydrogels from control, severe COPD [Global Initiative for Chronic Obstructive Lung Disease (GOLD) IV], and fibrotic human lung tissue and evaluate whether their stiffness and viscoelastic properties were reflective of native tissue. For hydrogel generation, control, COPD GOLD IV, and fibrotic human lung tissues were decellularized, lyophilized, ground into powder, porcine pepsin solubilized, buffered with PBS, and gelled at 37°C. Rheological properties from tissues and hydrogels were assessed with a low-load compression tester measuring the stiffness and viscoelastic properties in terms of a generalized Maxwell model representing phases of viscoelastic relaxation. The ECM hydrogels had a greater stress relaxation than tissues. ECM hydrogels required three Maxwell elements with slightly faster relaxation times (τ) than that of native tissue, which required four elements. The relative importance (Ri) of the first Maxwell element contributed the most in ECM hydrogels, whereas for tissue the contribution was spread over all four elements. IPF tissue had a longer-lasting fourth element with a higher Ri than the other tissues, and IPF ECM hydrogels did require a fourth Maxwell element, in contrast to all other ECM hydrogels. This study shows that hydrogels composed of native human lung ECM can be generated. Stiffness of ECM hydrogels resembled that of whole tissue, while viscoelasticity differed.

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