Expression of targets of the RNA-binding protein AUF-1 in human airway epithelium indicates its role in cellular senescence and inflammation DOI Creative Commons
Ilaria Salvato, Luca Ricciardi, Jessica Dal Col

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: July 7, 2023

Introduction The RNA-binding protein AU-rich-element factor-1 (AUF-1) participates to posttranscriptional regulation of genes involved in inflammation and cellular senescence, two pathogenic mechanisms chronic obstructive pulmonary disease (COPD). Decreased AUF-1 expression was described bronchiolar epithelium COPD patients versus controls vitro cytokine- cigarette smoke-challenged human airway epithelial cells, prompting the identification AUF-1-targeted transcripts function, investigation on mechanism its loss. Results RNA immunoprecipitation-sequencing (RIP-Seq) identified, cell line BEAS-2B, 494 AUF-1-bound mRNAs enriched their 3’-untranslated regions for a Guanine-Cytosine (GC)-rich binding motif. association with selected synthetic GC-rich motif were validated by biotin pulldown. AUF-1-targets’ steady-state levels equally affected partial or near-total loss induced cytomix (TNFα/IL1β/IFNγ/10 nM each) siRNA, respectively, differential transcript decay rates. Cytomix-mediated decrease BEAS-2B primary small-airways (HSAEC) replicated treatment senescence- inducer compound etoposide associated readouts cell-cycle arrest, increase lysosomal damage senescence-associated secretory phenotype (SASP) factors, transfer extracellular vesicles, detected transmission electron microscopy immunoblotting. Extensive in-silico genome ontology analysis found, consistent functions, RIP-Seq-derived AUF-1-targets COPD-related pathways inflammation, gene also public SASP proteome atlas; target signature significantly represented multiple transcriptomic databases generated from HSAEC, lung tissue single-cell RNA-sequencing, displaying predominant downregulation expression. Discussion Loss intracellular may alter targets particularly relevant protection genomic integrity regulation, thus concurring inflammatory responses related oxidative stress accelerated aging. Exosomal-associated turn preserve bound sustain participating spreading senescence neighbouring cells.

Language: Английский

The Complex Association between COPD and COVID-19 DOI Open Access
Nikhil T Awatade, Peter Wark, Andrew S. L. Chan

et al.

Journal of Clinical Medicine, Journal Year: 2023, Volume and Issue: 12(11), P. 3791 - 3791

Published: May 31, 2023

Chronic obstructive pulmonary disease (COPD) is significant cause of morbidity and mortality worldwide. There mounting evidence suggesting that COPD patients are at increased risk severe COVID-19 outcomes; however, it remains unclear whether they more susceptible to acquiring SARS-CoV-2 infection. In this comprehensive review, we aim provide an up-to-date perspective the intricate relationship between COVID-19. We conducted a thorough review literature examine regarding susceptibility infection severity their outcomes. While most studies have found pre-existing associated with worse outcomes, some yielded conflicting results. also discuss confounding factors such as cigarette smoking, inhaled corticosteroids, socioeconomic genetic may influence association. Furthermore, acute management, treatment, rehabilitation, recovery in how public health measures impact care. conclusion, while association complex requires further investigation, highlights need for careful management during pandemic minimize

Language: Английский

Citations

26
The persistent inflammation in COPD: is autoimmunity the core mechanism? DOI Creative Commons

Lingling Dong,

Zhengyuan Liu,

Kaijun Chen

et al.

European Respiratory Review, Journal Year: 2024, Volume and Issue: 33(171), P. 230137 - 230137

Published: Jan. 31, 2024

COPD poses a significant global public health challenge, primarily characterised by irreversible airflow restriction and persistent respiratory symptoms. The hallmark pathology of includes sustained airway inflammation the eventual destruction lung tissue structure. While multiple risk factors are implicated in disease's progression, underlying mechanisms remain largely elusive. perpetuation is pivotal to advancement COPD, emphasising importance investigating these self-sustaining for deeper understanding pathogenesis. Autoimmune responses constitute critical mechanism maintaining inflammation, with burgeoning evidence pointing their central role progression; yet, intricacies inadequately defined. This review elaborates on supporting presence autoimmune processes examines potential through which may drive chronic characteristic disease. Moreover, we attempt interpret clinical manifestations autoimmunity.

Language: Английский

Citations

10
Vitronectin regulates lung tissue remodeling and emphysema in chronic obstructive pulmonary disease DOI
Gang Liu, Alan Hsu,

Silke Geirnaert

et al.

Molecular Therapy, Journal Year: 2025, Volume and Issue: 33(3), P. 917 - 932

Published: Jan. 21, 2025

Language: Английский

Citations

1
COVID-19 and risk of long-term mortality in COPD: a nationwide population-based cohort study DOI Creative Commons
Hyun Lee, Sang Hyuk Kim, Cho Yun Jeong

et al.

BMJ Open Respiratory Research, Journal Year: 2025, Volume and Issue: 12(1), P. e002694 - e002694

Published: Feb. 1, 2025

Background Chronic obstructive pulmonary disease (COPD) is a risk factor for severe COVID-19. However, mortality after COVID-19 recovery in this population remains unclear. Methods We retrospectively enrolled individuals with COPD from the Korean National Health Insurance database. compared rate who recovered between 8 October 2020 and 31 December 2021 (COVID-19 cohort, n=2499) that 1:1 propensity score-matched controls (n=2499). The study was followed until either death or 30 September 2022, whichever came first. Results cohort had 4.8% vs 2.7% matched during median follow-up of 319 days (IQR, 293–422 days), including 14 time. higher than (adjusted HR (aHR)=1.81, 95% CI=1.35 to 2.45). notably (aHR=5.05, CI=3.65 6.97), especially first 180 (highest (aHR=20.25, CI=7.79 52.64)). Non-severe does not increase (aHR=0.85, CI=0.57 1.28). Conclusion Individuals recovering showed an increased long-term mortality, particularly within post-recovery, those experienced

Language: Английский

Citations

1
Mitochondria-Targeted Antioxidants as a Therapeutic Strategy for Chronic Obstructive Pulmonary Disease DOI Creative Commons
Lauren H. Fairley, Shatarupa Das, Vivek Dharwal

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(4), P. 973 - 973

Published: April 21, 2023

Oxidative stress is a major hallmark of COPD, contributing to inflammatory signaling, corticosteroid resistance, DNA damage, and accelerated lung aging cellular senescence. Evidence suggests that oxidative damage not solely due exogenous exposure inhaled irritants, but also endogenous sources oxidants in the form reactive oxygen species (ROS). Mitochondria, producers ROS, exhibit impaired structure function resulting reduced capacity excessive ROS production. Antioxidants have been shown protect against ROS-induced by reducing levels, inflammation, protecting development emphysema. However, currently available antioxidants are routinely used management suggesting need for more effective antioxidant agents. In recent years, number mitochondria-targeted (MTA) compounds developed capable crossing mitochondria lipid bilayer, offering targeted approach at its source. particular, MTAs illicit greater protective effects compared non-targeted, further apoptosis protection mtDNA they promising therapeutic agents treatment COPD. Here, we review evidence potential as chronic disease discuss current challenges future directions.

Language: Английский

Citations

21
Cathepsin B in cardiovascular disease: Underlying mechanisms and therapeutic strategies DOI Creative Commons

Zhulan Cai,

Shunyao Xu, Chen Liu

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2024, Volume and Issue: 28(17)

Published: Sept. 1, 2024

Abstract Cathepsin B (CTSB) is a member of the cysteine protease family, primarily responsible for degrading unnecessary organelles and proteins within acidic milieu lysosomes to facilitate recycling. Recent research has revealed that CTSB plays multifaceted role beyond its function as proteolytic enzyme in lysosomes. Importantly, recent data suggest significant impacts on different cardiac pathological conditions, such atherosclerosis (AS), myocardial infarction, hypertension, heart failure cardiomyopathy. Especially context AS, preclinical models clinical sample imaging indicate cathepsin activity‐based probe can reliably image activity foam cells atherosclerotic plaques; concurrently, it allows synchronous diagnostic therapeutic interventions. However, our knowledge cardiovascular disease still early stage. This paper aims provide comprehensive review significance physiology pathology, with objective laying theoretical groundwork development drugs targeting CTSB.

Language: Английский

Citations

8
The establishment of COPD organoids to study host-pathogen interaction reveals enhanced viral fitness of SARS-CoV-2 in bronchi DOI Creative Commons
Louisa L. Y. Chan, Danielle E. Anderson, Hong Sheng Cheng

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Dec. 10, 2022

Chronic obstructive pulmonary disease (COPD) is characterised by airflow limitation and infective exacerbations, however, in-vitro model systems for the study of host-pathogen interaction at individual level are lacking. Here, we describe establishment nasopharyngeal bronchial organoids from healthy individuals COPD that recapitulate level. In contrast to organoids, goblet cell hyperplasia reduced ciliary beat frequency were observed in hallmark features disease. Single-cell transcriptomics uncovered evidence altered cellular differentiation trajectories organoids. SARS-CoV-2 infection revealed more productive replication bronchi, key site severe COVID-19. Viral bacterial exposure induced greater pro-inflammatory responses summary, present an organoid recapitulates vivo physiological lung microenvironment amenable emerging infectious

Language: Английский

Citations

25
IL-33 Expression Is Lower in Current Smokers at both Transcriptomic and Protein Levels DOI Creative Commons
Alen Faiz, Rashad Mohammad Mahbub,

Fia Boedijono

et al.

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2023, Volume and Issue: 208(10), P. 1075 - 1087

Published: Sept. 14, 2023

IL-33 is a proinflammatory cytokine thought to play role in the pathogenesis of asthma and chronic obstructive pulmonary disease (COPD). A recent clinical trial using an anti-IL-33 antibody showed reduction exacerbation improved lung function ex-smokers but not current smokers with COPD.

Language: Английский

Citations

14
Lung Tissue Multi-Layer Network Analysis Uncovers the Molecular Heterogeneity of COPD DOI
Núria Olvera, Jon Sánchez-Valle, Iker Núñez‐Carpintero

et al.

American Journal of Respiratory and Critical Care Medicine, Journal Year: 2024, Volume and Issue: 210(10), P. 1219 - 1229

Published: April 16, 2024

Background. Chronic Obstructive Pulmonary Disease (COPD) is a heterogeneous condition. We hypothesized that the unbiased integration of different COPD lung omics using novel multi-layer approach may unravel mechanisms associated with clinical characteristics. Methods. profiled mRNA, miRNA and methylome in tissue samples from 135 former smokers COPD. For each omic (layer) we built patient network based on molecular similarity. The three networks were used to build network, optimization multiplex-modularity was employed identify communities across distinct layers. Uncovered related features. Results. identified five which molecularly characteristics, such as FEV1 blood eosinophils. Two (C#3 C#4) had both similarly low values emphysema, but different: C#3, not C#4, presented B T cell signatures downregulation secretory (SCGB1A1/SCGB3A1) ciliated cells. A machine learning model set up discriminate C#3 C#4 our cohort, validate them an independent cohort. Finally, spatial transcriptomics characterized small airway differences between identifying upregulation T/B homing chemokines, bacterial response genes C#3. Conclusions. analysis able clinically relevant communities. Patients emphysema can have airways immune patterns, indicating endotypes lead similar presentation.

Language: Английский

Citations

6
Cell Culture Differentiation and Proliferation Conditions Influence the In Vitro Regeneration of the Human Airway Epithelium DOI
Elisa Redman, Morgane Fierville,

Amélie Cavard

et al.

American Journal of Respiratory Cell and Molecular Biology, Journal Year: 2024, Volume and Issue: 71(3), P. 267 - 281

Published: June 6, 2024

The human airway mucociliary epithelium can be recapitulated

Language: Английский

Citations

5