scholarly journals Beyond the Genome: Epigenetic Mechanisms in Lung Remodeling

Physiology ◽  
2014 ◽  
Vol 29 (3) ◽  
pp. 177-185 ◽  
Author(s):  
James S. Hagood
Keyword(s):  
Noncoding Rna ◽  
Chromatin Modification ◽  
Cell Types ◽  
Chronic Obstructive ◽  
Epigenetic Mechanisms ◽  
Obstructive Pulmonary Disease ◽  
Lung Remodeling ◽  
Novel Treatments ◽  
Chronic Lung Diseases ◽  
Technological Advances

The lung develops from a very simple outpouching of the foregut into a highly complex, finely structured organ with multiple specialized cell types that are required for its normal physiological function. During both the development of the lung and its remodeling in the context of disease or response to injury, gene expression must be activated and silenced in a coordinated manner to achieve the tremendous phenotypic heterogeneity of cell types required for homeostasis and pathogenesis. Epigenetic mechanisms, consisting of DNA base modifications such as methylation, alteration of histones resulting in chromatin modification, and the action of noncoding RNA, control the regulation of information “beyond the genome” required for both lung modeling and remodeling. Epigenetic regulation is subject to modification by environmental stimuli, such as oxidative stress, infection, and aging, and is thus critically important in chronic remodeling disorders such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), bronchopulmonary dysplasia (BPD), and pulmonary hypertension (PH). Technological advances have made it possible to evaluate genome-wide epigenetic changes (epigenomics) in diseases of lung remodeling, clarifying existing pathophysiological paradigms and uncovering novel mechanisms of disease. Many of these represent new therapeutic targets. Advances in epigenomic technology will accelerate our understanding of lung development and remodeling, and lead to novel treatments for chronic lung diseases.

scholarly journals Signaling Control of Mucociliary Epithelia: Stem Cells, Cell Fates, and the Plasticity of Cell Identity in Development and Disease

2021 ◽  
pp. 1-18
Author(s):  
Peter Walentek
Keyword(s):  
Stem Cells ◽  
Mucociliary Clearance ◽  
Cell Types ◽  
Secretory Cells ◽  
Chronic Obstructive ◽  
Cell Identity ◽  
Obstructive Pulmonary Disease ◽  
Congenital Diseases ◽  
Inhaled Particles ◽  
Mucociliary Epithelia

Mucociliary epithelia are composed of multiciliated, secretory, and stem cells and line various organs in vertebrates such as the respiratory tract. By means of mucociliary clearance, those epithelia provide a first line of defense against inhaled particles and pathogens. Mucociliary clearance relies on the correct composition of cell types, that is, the proper balance of ciliated and secretory cells. A failure to generate and to maintain correct cell type composition and function results in impaired clearance and high risk to infections, such as in congenital diseases (e.g., ciliopathies) as well as in acquired diseases, including asthma, chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). While it remains incompletely resolved how precisely cell types are specified and maintained in development and disease, many studies have revealed important mechanisms regarding the signaling control in mucociliary cell types in various species. Those studies not only provided insights into the signaling contribution to organ development and regeneration but also highlighted the remarkable plasticity of cell identity encountered in mucociliary maintenance, including frequent trans-differentiation events during homeostasis and specifically in disease. This review will summarize major findings and provide perspectives regarding the future of mucociliary research and the treatment of chronic airway diseases associated with tissue remodeling.

scholarly journals Chronic Obstructive Pulmonary Disease: NHLBI Workshop on the Primary Prevention of Chronic Lung Diseases

2014 ◽  
Vol 11 (Supplement 3) ◽  
pp. S154-S160 ◽  
Author(s):  
M. Bradley Drummond ◽  
A. Sonia Buist ◽  
James D. Crapo ◽  
Robert A. Wise ◽  
Stephen I. Rennard
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Primary Prevention ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases

scholarly journals Does cystic fibrosis constitute an advantage in COVID-19 infection?

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Valentino Bezzerri ◽  
Francesca Lucca ◽  
Sonia Volpi ◽  
Marco Cipolli
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cystic Fibrosis ◽  
Lung Diseases ◽  
Respiratory Viruses ◽  
Chronic Obstructive ◽  
Veneto Region ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Italian Regions ◽  
Pulmonary Impairment

Abstract The Veneto region is one of the most affected Italian regions by COVID-19. Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), may constitute a risk factor in COVID-19. Moreover, respiratory viruses were generally associated with severe pulmonary impairment in cystic fibrosis (CF). We would have therefore expected numerous cases of severe COVID-19 among the CF population. Surprisingly, we found that CF patients were significantly protected against infection by SARS-CoV-2. We discussed this aspect formulating some reasonable theories.

scholarly journals Comprehensive Analysis of Transcriptome Sequencing Data in the Lung Tissues of COPD Subjects

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Woo Jin Kim ◽  
Jae Hyun Lim ◽  
Jae Seung Lee ◽  
Sang-Do Lee ◽  
Ju Han Kim ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Complex Disease ◽  
Chromatin Modification ◽  
Airflow Obstruction ◽  
Airflow Limitation ◽  
Chronic Obstructive ◽  
Sequencing Data ◽  
Obstructive Pulmonary Disease ◽  
Control Subjects ◽  
Expression Of Genes

Background and Objectives.Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airflow limitation. Although airway inflammation and oxidative stress are known to be important in the pathogenesis of COPD, the mechanism underlying airflow obstruction is not fully understood. Gene expression profiling of lung tissue was performed to define the molecular pathways that are dysregulated in COPD.Methods.RNA was isolated from lung tissues obtained from 98 subjects with COPD and 91 control subjects with normal spirometry. The RNA samples were processed with RNA-seq using the HiSeq 2000 system. Genes expressed differentially between the two groups were identified using Student’st-test.Results.After filtering for genes with zero counts and noncoding genes, 16,676 genes were evaluated. A total of 2312 genes were differentially expressed between the lung tissues of COPD and control subjects (false discovery rate correctedq<0.01). The expression of genes related to oxidative phosphorylation and protein catabolism was reduced and genes related to chromatin modification were dysregulated in lung tissues of COPD subjects.Conclusions. Oxidative phosphorylation, protein degradation, and chromatin modification were the most dysregulated pathways in the lung tissues of COPD subjects. These findings may have clinical and mechanistic implications in COPD.

scholarly journals Hallmarks of the ageing lung

2015 ◽  
Vol 45 (3) ◽  
pp. 807-827 ◽  
Author(s):  
Silke Meiners ◽  
Oliver Eickelberg ◽  
Melanie Königshoff
Keyword(s):  
Lung Cancer ◽  
Chronic Obstructive Pulmonary Disease ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Specific Effects ◽  
Chronic Lung Diseases

Ageing is the main risk factor for major non-communicable chronic lung diseases, including chronic obstructive pulmonary disease, most forms of lung cancer and idiopathic pulmonary fibrosis. While the prevalence of these diseases continually increases with age, their respective incidence peaks at different times during the lifespan, suggesting specific effects of ageing on the onset and/or pathogenesis of chronic obstructive pulmonary disease, lung cancer and idiopathic pulmonary fibrosis. Recently, the nine hallmarks of ageing have been defined as cell-autonomous and non-autonomous pathways involved in ageing. Here, we review the available evidence for the involvement of each of these hallmarks in the pathogenesis of chronic obstructive pulmonary disease, lung cancer, or idiopathic pulmonary fibrosis. Importantly, we propose an additional hallmark, “dysregulation of the extracellular matrix”, which we argue acts as a crucial modifier of cell-autonomous changes and functions, and as a key feature of the above-mentioned lung diseases.

scholarly journals Emerging concepts in smooth muscle contributions to airway structure and function: implications for health and disease

2016 ◽  
Vol 311 (6) ◽  
pp. L1113-L1140 ◽  
Author(s):  
Y. S. Prakash
Keyword(s):  
Smooth Muscle ◽  
Cell Types ◽  
Structure And Function ◽  
Normal Lung ◽  
Future Research ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Health And Disease ◽  
Growth And Aging ◽  
And Function

Airway structure and function are key aspects of normal lung development, growth, and aging, as well as of lung responses to the environment and the pathophysiology of important diseases such as asthma, chronic obstructive pulmonary disease, and fibrosis. In this regard, the contributions of airway smooth muscle (ASM) are both functional, in the context of airway contractility and relaxation, as well as synthetic, involving production and modulation of extracellular components, modulation of the local immune environment, cellular contribution to airway structure, and, finally, interactions with other airway cell types such as epithelium, fibroblasts, and nerves. These ASM contributions are now found to be critical in airway hyperresponsiveness and remodeling that occur in lung diseases. This review emphasizes established and recent discoveries that underline the central role of ASM and sets the stage for future research toward understanding how ASM plays a central role by being both upstream and downstream in the many interactive processes that determine airway structure and function in health and disease.

scholarly journals Muscarinic M3 receptors on structural cells regulate cigarette smoke-induced neutrophilic airway inflammation in mice

2015 ◽  
Vol 308 (1) ◽  
pp. L96-L103 ◽  
Author(s):  
Loes E. M. Kistemaker ◽  
Ronald P. van Os ◽  
Albertina Dethmers-Ausema ◽  
I. Sophie T. Bos ◽  
Machteld N. Hylkema ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cigarette Smoke ◽  
Neutrophil Migration ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Chronic Obstructive ◽  
Wild Type ◽  
Obstructive Pulmonary Disease ◽  
Neutrophilic Inflammation ◽  
Relative Contribution

Anticholinergics, blocking the muscarinic M3 receptor, are effective bronchodilators for patients with chronic obstructive pulmonary disease. Recent evidence from M3 receptor-deficient mice (M3R−/−) indicates that M3 receptors also regulate neutrophilic inflammation in response to cigarette smoke (CS). M3 receptors are present on almost all cell types, and in this study we investigated the relative contribution of M3 receptors on structural cells vs. inflammatory cells to CS-induced inflammation using bone marrow chimeric mice. Bone marrow chimeras (C56Bl/6 mice) were generated, and engraftment was confirmed after 10 wk. Thereafter, irradiated and nonirradiated control animals were exposed to CS or fresh air for four consecutive days. CS induced a significant increase in neutrophil numbers in nonirradiated and irradiated control animals (4- to 35-fold). Interestingly, wild-type animals receiving M3R−/− bone marrow showed a similar increase in neutrophil number (15-fold). In contrast, no increase in the number of neutrophils was observed in M3R−/− animals receiving wild-type bone marrow. The increase in keratinocyte-derived chemokine (KC) levels was similar in all smoke-exposed groups (2.5- to 5.0-fold). Microarray analysis revealed that fibrinogen-α and CD177, both involved in neutrophil migration, were downregulated in CS-exposed M3R−/− animals receiving wild-type bone marrow compared with CS-exposed wild-type animals, which was confirmed by RT-qPCR (1.6–2.5 fold). These findings indicate that the M3 receptor on structural cells plays a proinflammatory role in CS-induced neutrophilic inflammation, whereas the M3 receptor on inflammatory cells does not. This effect is probably not mediated via KC release, but may involve altered adhesion and transmigration of neutrophils via fibrinogen-α and CD177.

scholarly journals Deregulated angiogenesis in chronic lung diseases: a possible role for lung mesenchymal progenitor cells (2017 Grover Conference Series)

2017 ◽  
Vol 8 (1) ◽  
pp. 204589321773980 ◽  
Author(s):  
Jonathan A. Kropski ◽  
Bradley W. Richmond ◽  
Christa F. Gaskill ◽  
Robert F. Foronjy ◽  
Susan M. Majka
Keyword(s):  
Progenitor Cells ◽  
Lung Diseases ◽  
Normal Function ◽  
Interstitial Lung Diseases ◽  
Chronic Obstructive ◽  
Mesenchymal Progenitor Cells ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Co Morbidity ◽  
Progression Of Disease

Chronic lung disease (CLD), including pulmonary fibrosis (PF) and chronic obstructive pulmonary disease (COPD), is the fourth leading cause of mortality worldwide. Both are debilitating pathologies that impede overall tissue function. A common co-morbidity in CLD is vasculopathy, characterized by deregulated angiogenesis, remodeling, and loss of microvessels. This substantially worsens prognosis and limits survival, with most current therapeutic strategies being largely palliative. The relevance of angiogenesis, both capillary and lymph, to the pathophysiology of CLD has not been resolved as conflicting evidence depicts angiogenesis as both reparative or pathologic. Therefore, we must begin to understand and model the underlying pathobiology of pulmonary vascular deregulation, alone and in response to injury induced disease, to define cell interactions necessary to maintain normal function and promote repair. Capillary and lymphangiogenesis are deregulated in both PF and COPD, although the mechanisms by which they co-regulate and underlie early pathogenesis of disease are unknown. The cell-specific mechanisms that regulate lung vascular homeostasis, repair, and remodeling represent a significant gap in knowledge, which presents an opportunity to develop targeted therapies. We have shown that that ABCG2pos multipotent adult mesenchymal stem or progenitor cells (MPC) influence the function of the capillary microvasculature as well as lymphangiogenesis. A balance of both is required for normal tissue homeostasis and repair. Our current models suggest that when lymph and capillary angiogenesis are out of balance, the non-equivalence appears to support the progression of disease and tissue remodeling. The angiogenic regulatory mechanisms underlying CLD likely impact other interstitial lung diseases, tuberous sclerosis, and lymphangioleiomyomatosis.

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