scholarly journals Increased LGR6 Expression Sustains Long-Term Wnt Activation and Acquisition of Senescence in Epithelial Progenitors in Chronic Lung Diseases

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3437
Author(s):  
Emanuela E. Cortesi ◽  
Bob Meeusen ◽  
Arno Vanstapel ◽  
Stijn E. Verleden ◽  
Bart M. Vanaudenaerde ◽  
...  
Keyword(s):  
Lung Diseases ◽  
The Elderly ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Normal Tissues ◽  
Chronic Lung Diseases ◽  
Major Increase ◽  
Aberrant Regeneration ◽  
Chronic Activation ◽  
Canonical Wnt

Chronic lung diseases (CLDs) represent a set of disorders characterized by the progressive loss of proper lung function. Among severe CLDs, the incidence of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) has grown over the last decades, mainly in the elderly population. Several studies have highlighted an increased expression of senescence-related markers in the resident progenitor cells in COPD and IPF, possibly undermining epithelial integrity and contributing to the progression and the aggravation of both diseases. Recently, the chronic activation of the canonical Wnt/β-catenin pathway was shown to induce cellular senescence. Here, we investigated the localization and the expression of leucin-rich repeat-containing G-protein-coupled receptor 6 (LGR6), a protein that activates and potentiates the canonical Wnt signalling. Through immunohistochemical analyses, we identified a lesion-associated rise in LGR6 levels in abnormal lung epithelial progenitors in COPD and IPF when compared to histologically normal tissues. Moreover, in areas of aberrant regeneration, chronic damage and fibrosis, LGR6-expressing epithelial progenitors displayed a major increase in the expression of senescence-associated markers. Our study suggests the involvement of LGR6 in the chronic activation of the Wnt/β-catenin pathway, mediating the impairment and exhaustion of epithelial progenitors in COPD and IPF.

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 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 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.

scholarly journals COVID-19 and restrictive lung disease: A deadly combo to trip off the fine balance

2020 ◽  
Vol 90 (2) ◽  
Author(s):  
Kamal Kant Sahu ◽  
Ajay Kumar Mishra ◽  
Kevin Martin ◽  
Iryna Chastain
Keyword(s):  
Risk Factors ◽  
Chronic Obstructive Pulmonary Disease ◽  
Risk Factor ◽  
Lung Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Immunocompromised Patients ◽  
Obstructive Pulmonary Disease ◽  
Restrictive Lung Disease ◽  
Chronic Lung Diseases

Coronavirus Disease (COVID-19) pandemic has so far led to innumerable deaths worldwide. The risk factors so far that have been most studied as poor prognostic factors are old age, individuals with multiple comorbidities and immunocompromised patients. Amongst the chronic lung diseases, most patients with COVID-19 reported so far had asthma, chronic obstructive pulmonary disease (COPD), and interstitial lung disease. Herein, we discuss the significance of restrictive lung disease during the COVID-19 pandemic as a potential risk factor via an example of a patient with kyphoscoliosis who succumbed to death due to COVID-19 pneumonia.

scholarly journals The Serpin Superfamily and Their Role in the Regulation and Dysfunction of Serine Protease Activity in COPD and Other Chronic Lung Diseases

2021 ◽  
Vol 22 (12) ◽  
pp. 6351
Author(s):  
Gillian A. Kelly-Robinson ◽  
James A. Reihill ◽  
Fionnuala T. Lundy ◽  
Lorcan P. McGarvey ◽  
John C. Lockhart ◽  
...  
Keyword(s):  
Serine Protease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Stable Form ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Mechanism Of Inhibition ◽  
Serine Protease Activity ◽  
Alpha 1 Antitrypsin ◽  
The Relationship

Chronic obstructive pulmonary disease (COPD) is a debilitating heterogeneous disease characterised by unregulated proteolytic destruction of lung tissue mediated via a protease-antiprotease imbalance. In COPD, the relationship between the neutrophil serine protease, neutrophil elastase, and its endogenous inhibitor, alpha-1-antitrypsin (AAT) is the best characterised. AAT belongs to a superfamily of serine protease inhibitors known as serpins. Advances in screening technologies have, however, resulted in many members of the serpin superfamily being identified as having differential expression across a multitude of chronic lung diseases compared to healthy individuals. Serpins exhibit a unique suicide-substrate mechanism of inhibition during which they undergo a dramatic conformational change to a more stable form. A limitation is that this also renders them susceptible to disease-causing mutations. Identification of the extent of their physiological/pathological role in the airways would allow further expansion of knowledge regarding the complexity of protease regulation in the lung and may provide wider opportunity for their use as therapeutics to aid the management of COPD and other chronic airways diseases.

scholarly journals Venous Thromboembolic Disease in Chronic Inflammatory Lung Diseases: Knowns and Unknowns

2021 ◽  
Vol 10 (10) ◽  
pp. 2061
Author(s):  
George Keramidas ◽  
Konstantinos I. Gourgoulianis ◽  
Ourania S. Kotsiou
Keyword(s):  
Lung Diseases ◽  
Thrombotic Event ◽  
Interstitial Lung Diseases ◽  
Chronic Obstructive ◽  
Predisposing Factor ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Increased Risk ◽  
Chronic Pulmonary Diseases ◽  
The Relationship

Persistent inflammation within the respiratory tract underlies the pathogenesis of numerous chronic pulmonary diseases. There is evidence supporting that chronic lung diseases are associated with a higher risk of venous thromboembolism (VTE). However, the relationship between lung diseases and/or lung function with VTE is unclear. Understanding the role of chronic lung inflammation as a predisposing factor for VTE may help determine the optimal management and aid in the development of future preventative strategies. We aimed to provide an overview of the relationship between the most common chronic inflammatory lung diseases and VTE. Asthma, chronic obstructive pulmonary disease, interstitial lung diseases, or tuberculosis increase the VTE risk, especially pulmonary embolism (PE), compared to the general population. However, high suspicion is needed to diagnose a thrombotic event early as the clinical presentation inevitably overlaps with respiratory disorders. PE risk increases with disease severity and exacerbations. Hence, hospitalized patients should be considered for thromboprophylaxis administration. Conversely, all VTE patients should be asked for lung comorbidities before determining anticoagulant therapy duration, as those patients are at increased risk of recurrent PE episodes rather than DVT. Further research is needed to understand the underlying pathophysiology of in-situ thrombosis in those patients.

scholarly journals Metabolic reprogramming in the pathogenesis of chronic lung diseases, including BPD, COPD, and pulmonary fibrosis

2018 ◽  
Vol 314 (4) ◽  
pp. L544-L554 ◽  
Author(s):  
Haifeng Zhao ◽  
Phyllis A. Dennery ◽  
Hongwei Yao
Keyword(s):  
Fatty Acids ◽  
Pulmonary Fibrosis ◽  
Lung Diseases ◽  
Cellular Proliferation ◽  
Inflammatory Responses ◽  
Tricarboxylic Acid Cycle ◽  
Metabolic Reprogramming ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases

The metabolism of nutrient substrates, including glucose, glutamine, and fatty acids, provides acetyl-CoA for the tricarboxylic acid cycle to generate energy, as well as metabolites for the biosynthesis of biomolecules, including nucleotides, proteins, and lipids. It has been shown that metabolism of glucose, fatty acid, and glutamine plays important roles in modulating cellular proliferation, differentiation, apoptosis, autophagy, senescence, and inflammatory responses. All of these cellular processes contribute to the pathogenesis of chronic lung diseases, including bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and pulmonary fibrosis. Recent studies demonstrate that metabolic reprogramming occurs in patients with and animal models of chronic lung diseases, suggesting that metabolic dysregulation may participate in the pathogenesis and progression of these diseases. In this review, we briefly discuss the catabolic pathways for glucose, glutamine, and fatty acids, and focus on how metabolic reprogramming of these pathways impacts cellular functions and leads to the development of these chronic lung diseases. We also highlight how targeting metabolic pathways can be utilized in the prevention and treatment of these diseases.

SLPI and trappin-2 as therapeutic agents to target airway serine proteases in inflammatory lung diseases: current and future directions

2011 ◽  
Vol 39 (5) ◽  
pp. 1441-1446 ◽  
Author(s):  
Marie-Louise Zani ◽  
Annabelle Tanga ◽  
Ahlame Saidi ◽  
Hélène Serrano ◽  
Sandrine Dallet-Choisy ◽  
...  
Keyword(s):  
Serine Proteases ◽  
Lung Diseases ◽  
Therapeutic Potential ◽  
Therapeutic Agents ◽  
Cathepsin G ◽  
Chronic Obstructive ◽  
Inhaled Drugs ◽  
Future Directions ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases

It is now clear that NSPs (neutrophil serine proteases), including elastase, Pr3 (proteinase 3) and CatG (cathepsin G) are major pathogenic determinants in chronic inflammatory disorders of the lungs. Two unglycosylated natural protease inhibitors, SLPI (secretory leucocyte protease inhibitor) and elafin, and its precursor trappin-2 that are found in the lungs, have therapeutic potential for reducing the protease-induced inflammatory response. This review examines the multifaceted roles of SLPI and elafin/trappin-2 in the context of their possible use as inhaled drugs for treating chronic lung diseases such as CF (cystic fibrosis) and COPD (chronic obstructive pulmonary disease).

scholarly journals Aging and Lung Disease

2020 ◽  
Vol 82 (1) ◽  
pp. 433-459 ◽  
Author(s):  
Soo Jung Cho ◽  
Heather W. Stout-Delgado
Keyword(s):  
Lung Diseases ◽  
Chronic Obstructive ◽  
Regenerative Capacity ◽  
Obstructive Pulmonary Disease ◽  
Susceptibility To Infection ◽  
Chronic Lung Diseases ◽  
Progression Of Disease ◽  
Pulmonary Remodeling ◽  
Increased Susceptibility ◽  
Lung Aging

People worldwide are living longer, and it is estimated that by 2050, the proportion of the world's population over 60 years of age will nearly double. Natural lung aging is associated with molecular and physiological changes that cause alterations in lung function, diminished pulmonary remodeling and regenerative capacity, and increased susceptibility to acute and chronic lung diseases. As the aging population rapidly grows, it is essential to examine how alterations in cellular function and cell-to-cell interactions of pulmonary resident cells and systemic immune cells contribute to a higher risk of increased susceptibility to infection and development of chronic diseases, such as chronic obstructive pulmonary disease and interstitial pulmonary fibrosis. This review provides an overview of physiological, structural, and cellular changes in the aging lung and immune system that facilitate the development and progression of disease.

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