Recent evidence from omic analysis for redox signalling and mitochondrial oxidative stress in COPD

Mumby, Sharon; Adcock, Ian M.

doi:10.1186/s12950-022-00308-9

Cited by 22 publications

(23 citation statements)

References 112 publications

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“…In the airways, the lungs and blood of COPD patients show mitochondrial morphological alterations, mitochondrial dysfunction, and increased ROS levels. 393 The mitochondriaspecific antioxidant mitoQ can reduce airway smooth muscle cell inflammation and the airway response. 394 Mitochondrial autophagy is also deficient in COPD patients.…”

Section: Osteoarthritis (Oa)mentioning

confidence: 99%

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Guo

Huang

Dou

et al. 2022

Sig Transduct Target Ther

350

160

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Aging is a gradual and irreversible pathophysiological process. It presents with declines in tissue and cell functions and significant increases in the risks of various aging-related diseases, including neurodegenerative diseases, cardiovascular diseases, metabolic diseases, musculoskeletal diseases, and immune system diseases. Although the development of modern medicine has promoted human health and greatly extended life expectancy, with the aging of society, a variety of chronic diseases have gradually become the most important causes of disability and death in elderly individuals. Current research on aging focuses on elucidating how various endogenous and exogenous stresses (such as genomic instability, telomere dysfunction, epigenetic alterations, loss of proteostasis, compromise of autophagy, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, deregulated nutrient sensing) participate in the regulation of aging. Furthermore, thorough research on the pathogenesis of aging to identify interventions that promote health and longevity (such as caloric restriction, microbiota transplantation, and nutritional intervention) and clinical treatment methods for aging-related diseases (depletion of senescent cells, stem cell therapy, antioxidative and anti-inflammatory treatments, and hormone replacement therapy) could decrease the incidence and development of aging-related diseases and in turn promote healthy aging and longevity.

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Section: Osteoarthritis (Oa)mentioning

confidence: 99%

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Guo

Huang

Dou

et al. 2022

Sig Transduct Target Ther

350

160

View full text Add to dashboard Cite

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“…Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of mortality worldwide ( 1 ). Oxidative stress (OS) is one of the most important factors contributing to the pathogenesis and severity of COPD ( 2 , 3 ). COPD is a heterogeneous disease with several potentially treatable traits that have been associated with disease prognosis ( 4 ) including muscle weakness ( 5 ), reduced exercise capacity ( 6 ), and increased oxygen desaturation (OD) during exercise ( 7 ).…”

Section: Introductionmentioning

confidence: 99%

Circulating levels of mitochondrial oxidative stress-related peptides MOTS-c and Romo1 in stable COPD: A cross-sectional study

et al. 2023

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BackgroundMOTS-c and Romo1 are mitochondrial peptides that are modulated by oxidative stress. No previous studies have explored circulating levels of MOTS-c in patients with chronic obstructive pulmonary disease (COPD).MethodsWe enrolled 142 patients with stable COPD and 47 smokers with normal lung function in an observational cross-sectional study. We assessed serum levels of both MOTS-c and Romo1 and associated these findings with clinical characteristics of COPD.ResultsCompared with smokers with normal lung function, patients with COPD had lower levels of MOTS-c (p = 0.02) and higher levels of Romo1 (p = 0.01). A multivariate logistic regression analysis revealed that above-median MOTS-c levels were positively associated with Romo1 levels (OR 1.075, 95% CI 1.005–1.150, p = 0.036), but no association was found with other COPD characteristics. Below-median levels of circulating MOTS-c were associated with oxygen desaturation (OR 3.25 95% CI 1.456–8.522, p = 0.005) and walking <350 meters (OR 3.246 95% CI 1.229–8.577, p = 0.018) in six-minute walk test. Above-median levels of Romo1 were positively associated with current smoking (OR 2.756, 95% CI 1.133–6.704, p = 0.025) and negatively associated with baseline oxygen saturation (OR 0.776 95% CI 0.641–0.939, p = 0.009).ConclusionsReduced levels of circulating MOTS-c and increased levels of Romo1 were detected in patients diagnosed with COPD. Low levels of MOTS-c were associated with oxygen desaturation and poorer exercise capacity using 6 min walk test. Romo1 was associated with current smoking and baseline oxygen saturation.Trial registrationwww.clinicaltrials.gov; No.: NCT04449419; URL: www.clinicaltrials.gov. Date of registration: June 26, 2020.

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“…Both FoxO and TGF-β have been linked to cancer pathogenesis, with the former being a positive mediator of cell growth (77) and vascular remodeling (41) and the latter having both tumor suppressing and promoting functions (78). Studies have shown decreased levels of the FoxO protein in COPD (41, 79-81). Di Stefano et al found that, compared to controls, COPD peripheral airway samples have decreased TGF-β1 + and TGF-β3 + bronchial epithelial cells (82).…”

Section: Discussionmentioning

confidence: 99%

Lung transcriptomics of radiologic emphysema reveal barrier function impairment and macrophage M1-M2 imbalance

Gregory

Suryadevara

et al. 2022

Preprint

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RationaleWhile many studies have examined gene expression in lung tissue, the gene regulatory processes underlying emphysema are still not well understood. Finding efficient non-imaging screening methods and disease-modifying therapies has been challenging, but knowledge of the transcriptomic features of emphysema may help in this effort.ObjectivesOur goals were to identify emphysema-associated biological pathways through transcriptomic analysis of bulk lung tissue, to determine the lung cell types in which these emphysema-associated pathways are altered, and to detect unique and overlapping transcriptomic signatures in blood and lung.MethodsUsing RNA-sequencing data from 456 samples in the Lung Tissue Research Consortium and 2,370 blood samples from the COPDGene study, we examined the transcriptomic features of computed tomography quantified emphysema. We also queried lung single-cell RNA-sequencing data to identify cell types showing COPD-associated differential expression of the emphysema pathways found in the bulk analyses.Measurements and Main ResultsIn the lung, 1,055 differentially expressed genes and 29 dysregulated pathways were significantly associated with emphysema. We observed alternative splicing of genes regulating NF-κB and cell adhesion and increased activity in the TGF-β and FoxO signaling pathways. Multiple lung cell types displayed dysregulation of epithelial barrier function pathways, and an imbalance between pro-inflammatory M1 and anti-inflammatory M2 macrophages was detected. Lung tissue and blood samples shared 251 differentially expressed genes and two pathways (oxidative phosphorylation and ribosomal function).ConclusionsThis study identified emphysema-related changes in gene expression and alternative splicing, cell-type specific dysregulated pathways, and instances of shared pathway dysregulation between blood and lung.AT A GLANCE COMMENTARYScientific Knowledge on the SubjectPrior studies have investigated the transcriptomic characteristics of emphysema and its associated biological pathways. However, less is known about alternative splicing mechanisms and cell-type specific transcriptional patterns in emphysema. Additionally, a comparison between dysregulated genes and pathways in blood and lung tissues is needed to better understand the utility of non-invasive diagnostic and prognostic tools for emphysema.What This Study Adds to the FieldUsing lung samples from the Lung Tissue Research Consortium (LTRC) and blood samples from the COPDGene study, we performed differential gene and alternative splicing association analyses for CT-quantified emphysema. We then queried a previously published lung tissue single-cell RNA-sequencing atlas of COPD patients and controls to determine lung cell-type specific expression patterns of the biological pathways identified from the bulk analyses. We demonstrated that multiple pathways, including oxidative phosphorylation and ribosomal function processes, were enriched in both blood and lung tissues. We also observed that in COPD, oxidative phosphorylation was downregulated in pro-inflammatory (M1) macrophages and upregulated in anti-inflammatory (M2) macrophages. Additionally, other immunity-related cell types, including plasma cells, natural killer cells, and T lymphocytes, were linked to epithelial barrier function, such as the Rap1, adherens junction, and TGF-β signaling pathways.

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Recent evidence from omic analysis for redox signalling and mitochondrial oxidative stress in COPD

Cited by 22 publications

References 112 publications

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Aging and aging-related diseases: from molecular mechanisms to interventions and treatments

Circulating levels of mitochondrial oxidative stress-related peptides MOTS-c and Romo1 in stable COPD: A cross-sectional study

Lung transcriptomics of radiologic emphysema reveal barrier function impairment and macrophage M1-M2 imbalance

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