Noncanonical Wnt planar cell polarity signaling in lung development and disease

2020 ◽  
Vol 48 (1) ◽  
pp. 231-243 ◽  
Author(s):  
Eszter K. Vladar ◽  
Melanie Königshoff
Keyword(s):  
Cell Polarity ◽  
Lung Diseases ◽  
Planar Cell Polarity ◽  
Protein Complexes ◽  
Branching Morphogenesis ◽  
The Body ◽  
Pulmonary Vasculature ◽  
Chronic Obstructive ◽  
Beta Catenin ◽  
Chronic Lung Diseases

The planar cell polarity (PCP) signaling pathway is a potent developmental regulator of directional cell behaviors such as migration, asymmetric division and morphological polarization that are critical for shaping the body axis and the complex three-dimensional architecture of tissues and organs. PCP is considered a noncanonical Wnt pathway due to the involvement of Wnt ligands and Frizzled family receptors in the absence of the beta-catenin driven gene expression observed in the canonical Wnt cascade. At the heart of the PCP mechanism are protein complexes capable of generating molecular asymmetries within cells along a tissue-wide axis that are translated into polarized actin and microtubule cytoskeletal dynamics. PCP has emerged as an important regulator of developmental, homeostatic and disease processes in the respiratory system. It acts along other signaling pathways to create the elaborately branched structure of the lung by controlling the directional protrusive movements of cells during branching morphogenesis. PCP operates in the airway epithelium to establish and maintain the orientation of respiratory cilia along the airway axis for anatomically directed mucociliary clearance. It also regulates the establishment of the pulmonary vasculature. In adult tissues, PCP dysfunction has been linked to a variety of chronic lung diseases such as cystic fibrosis, chronic obstructive pulmonary disease, and idiopathic pulmonary arterial hypertension, stemming chiefly from the breakdown of proper tissue structure and function and aberrant cell migration during regenerative wound healing. A better understanding of these (impaired) PCP mechanisms is needed to fully harness the therapeutic opportunities of targeting PCP in chronic lung diseases.

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 THE MICROBIOTA OF LOWER AIRWAYS IN PATIENTS WITH CHRONIC OBSTRUCTIVE LUNG DISEASES

2018 ◽  
pp. 53-60
Author(s):  
S. A. Mazurina ◽  
G. A. Danilina ◽  
M. Yu. Smirnova ◽  
G. L. Osipova ◽  
V. B. Gervazieva ◽  
...  
Keyword(s):  
Burkholderia Cepacia ◽  
Lung Diseases ◽  
Morphological Changes ◽  
Bacterial Species ◽  
Chronic Obstructive Lung Disease ◽  
Induced Sputum ◽  
Chronic Obstructive ◽  
Obstructive Lung Diseases ◽  
Chronic Lung Diseases ◽  
Detection Frequency

Aim. We aimed to estimate the composition and the detection frequency of bacterial species in induced sputum samples from patients with bronchial asthma (BA), chronic obstructive lung disease (COPD) and its combined phenotype (ACOS). Materials and methods. Bacteriological examination of samples of induced sputum in patients with chronic obstructive pulmonary diseases (BA, COPD) was carried out. Results. Patients with asthma-COPD overlap syndrome exhibit more diverse bacterial species composition as represented both by gram-positive Streptococcus sрp., Staphylococcus spр., gram-negative Klebsiella pneumoniaе, Escherichia coli, Serratia marcescens, Pseudomonas aeruginosa, Haemophilus influenzae, Burkholderia cepacia and rodlike bacterium Corynebacterium spр., Actinomyces spр. и Tsukamurella рaurometabola as compared to patients with only one diagnosis of COPD or asthma. In addition, we revealed the differences between microbiological diversity and predominance of Streptococcus spр, Neisseria subflava with decrease of Enterococcus sрр. in samples from patients with complicated forms of obstructive lung diseases as COPD and ACOS, with pulmonary emphysema and/or pneumosclerosis. Conclusion. The biodiversity of lung microbiome could be one of the pathology risk factors in patients with chronic lung diseases, on the other hand reflecting the structural morphological changes in the lung tissue as a result of sustainable inflammation.

scholarly journals Nonantibiotic macrolides restore airway macrophage phagocytic function with potential anti-inflammatory effects in chronic lung diseases

2017 ◽  
Vol 312 (5) ◽  
pp. L678-L687 ◽  
Author(s):  
Sandra Hodge ◽  
Hai B. Tran ◽  
Rhys Hamon ◽  
Eugene Roscioli ◽  
Greg Hodge ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Lung Diseases ◽  
Bacterial Resistance ◽  
Scavenger Receptor ◽  
Lower Airway ◽  
Chronic Obstructive ◽  
Apoptotic Cells ◽  
Nontypeable Haemophilus Influenzae ◽  
Pyrin Domain ◽  
Chronic Lung Diseases

We reported defective efferocytosis associated with cigarette smoking and/or airway inflammation in chronic lung diseases, including chronic obstructive pulmonary disease, severe asthma, and childhood bronchiectasis. We also showed defects in phagocytosis of nontypeable Haemophilus influenzae (NTHi), a common colonizer of the lower airway in these diseases. These defects could be substantially overcome with low-dose azithromycin; however, chronic use may induce bacterial resistance. The aim of the present study was therefore to investigate two novel macrolides—2′-desoxy-9-(S)-erythromycylamine (GS-459755) and azithromycin-based 2′-desoxy molecule (GS-560660)—with significantly diminished antibiotic activity against Staphylococcus aureus, Streptococcus pneumonia, Moraxella catarrhalis, and H. influenzae. We tested their effects on efferocytosis, phagocytosis of NTHi, cell viability, receptors involved in recognition of apoptotic cells and/or NTHi (flow cytometry), secreted and cleaved intracellular IL-1β (cytometric bead array, immunofluorescence/confocal microscopy), and nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) using primary alveolar macrophages and THP-1 macrophages ± 10% cigarette smoke extract. Dose-response experiments showed optimal prophagocytic effects of GS-459755 and GS-560660 at concentrations of 0.5–1 µg/ml compared with our findings with azithromycin. Both macrolides significantly improved phagocytosis of apoptotic cells and NTHi (e.g., increases in efferocytosis and phagocytosis of NTHi: GS-459755, 23 and 22.5%, P = 0.043; GS-560660, 23.5 and 22%, P = 0.043, respectively). Macrophage viability remained >85% following 24 h exposure to either macrolide at concentrations up to 20 µg/ml. Secreted and intracellular-cleaved IL-1β was decreased with both macrolides with no significant changes in recognition molecules c-mer proto-oncogene tyrosine kinase; scavenger receptor class A, member 1; Toll-like receptor 2/4; or CD36. Particulate cytoplasmic immunofluorescence of NLRP3 inflammasome was also reduced significantly. We conclude that GS-459755 and GS-560660 may be useful for reducing airway inflammation in chronic lung diseases without inducing bacterial resistance.

824 Case Series on the Use of Volume Assured Pressure Support in Patients with Chronic Pulmonary Disease and Progressive Hypercapnia

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A321-A322
Author(s):  
William LeMaster ◽  
Dale Jun ◽  
Sharon De Cruz ◽  
Michelle Zeidler ◽  
Rajan Saggar
Keyword(s):  
Respiratory Failure ◽  
Lung Disease ◽  
Pulmonary Disease ◽  
Lung Diseases ◽  
Lung Transplant ◽  
Pressure Support ◽  
Case Series ◽  
Chronic Obstructive ◽  
Hypoxemic Respiratory Failure ◽  
Chronic Lung Diseases

Abstract Introduction Chronic hypercapnia results from destruction of lung parenchyma which occurs in chronic lung diseases including interstitial lung disease (ILD), bronchiectasis, and chronic lung transplant rejection. Many patients with these diseases will experience progressive respiratory failure eventually requiring consideration of transplantation or re-transplantation. Due to physiologic changes in sleep including reduction in tidal volume, worsening air tapping, and REM atonia, hypoventilation can be exacerbated during the sleeping hours. We present four patients who were prescribed nocturnal Volume Assured Pressure Support VAPS for their progressive hypercapnia. Report of case(s) Subject 1 is a 72 year old female with severe bronchiectasis and restrictive lung disease due to TB pneumonia at a young age. Subject 2 is a 45 year old male with history of pulmonary cavitation due to extensive TB disease when he was younger. Subject 3 is a 45-year-old woman with rheumatoid arthritis related ILD with associated pulmonary arterial hypertension. Subject 4 is a 74 year old patient with a bilateral lung transplant for IPF complicated by bronchiolitis obliterans syndrome who presented with progressive dyspnea and hypercapnia. Despite optimal therapy, all of these patients were admitted for hypercapnic and hypoxemic respiratory failure requiring treatment with BPAP then transitioned to nocturnal VAPS on discharge. For all patients, dyspnea and pCO2 improved as outpatients although all patients did eventually experience an exacerbation of their lung disease requiring repeat admission. Conclusion Due to the physiologic changes that occur with sleep, patients with severe lung disease may experience worsening CO2 retention while sleeping. There is little data assessing the use of chronic nocturnal non-invasive ventilation (NIV) to treat the hypercapnia of chronic lung diseases other than chronic obstructive pulmonary disease, extra-thoracic restriction, and neuromuscular disease. In this case series, nocturnal VAPS stabilized and/or reduced pCO2 in patients with pulmonary parenchymal disease of various etiologies. Additional studies are needed to assess long term effects of VAPS in these patients, including exacerbations, symptoms, and overall mortality. Support (if any):

scholarly journals Two-hybrid screening of FAM13A protein partners in lung epithelial cells

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
Manon Ruffin ◽  
Kristin E. Thompson ◽  
Harriet Corvol ◽  
Loic Guillot
Keyword(s):  
Lung Cancer ◽  
Lung Diseases ◽  
Sequence Similarity ◽  
Lung Epithelial Cells ◽  
Human Lung Cancer ◽  
Chronic Obstructive ◽  
Chronic Lung Diseases ◽  
Protein Partners ◽  
Two Hybrid ◽  
Hybrid Screening

Abstract Objectives Family with sequence similarity 13 member A (FAM13A) genetic variants have been associated with several chronic respiratory diseases including chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), idiopathic pulmonary fibrosis (IPF) and lung cancer. The FAM13A protein includes a RhoGTPase activating protein (RhoGAP) domain known to participate in various cellular mechanisms including cell proliferation. While intensive genomic studies have been performed to reveal its involvement in lung diseases, the biological role of FAM13A protein is still not completely elucidated. Results We therefore performed a two-hybrid screening to identify protein partners of FAM13A using a human lung cancer cDNA library. We identified several protein partners with a high confidence score. Researchers in the field of chronic lung diseases may benefit from this two-hybrid screening data which may reveal new research pathways to decipher.

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 Ancestral roles of atypical cadherins in planar cell polarity

2020 ◽  
Vol 117 (32) ◽  
pp. 19310-19320
Author(s):  
Maria Brooun ◽  
Alexander Klimovich ◽  
Mikhail Bashkurov ◽  
Bret J. Pearson ◽  
Robert E. Steele ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Polarity ◽  
Planar Cell Polarity ◽  
Sister Group ◽  
The Body ◽  
Cell Alignment ◽  
Actin Organization ◽  
Tissue Organization ◽  
Ancestral Function ◽  
Local Cell

Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins inHydra, a member of phylum Cnidaria a sister group of bilaterian. We foundHydradoes not possess a true Fat homolog, but has homologs of Fat-like (HyFatl) and Dachsous (HyDs) that localize at the apical membrane of ectodermal epithelial cells and are planar polarized perpendicular to the oral–aboral axis of the animal. Using a knockdown approach we found that HyFatl is involved in local cell alignment and cell–cell adhesion, and that reduction of HyFatl leads to defects in tissue organization in the body column. Overexpression and knockdown experiments indicate that the intracellular domain (ICD) of HyFatl affects actin organization through proline-rich repeats. Thus, planar polarization of Fat-like and Dachsous cadherins has ancient, prebilaterian origins, and Fat-like cadherins have ancient roles in cell adhesion, spindle orientation, and tissue organization.

scholarly journals Vitamin D Deficiency and Chronic Lung Disease

2009 ◽  
Vol 16 (3) ◽  
pp. 75-80 ◽  
Author(s):  
Christopher R Gilbert ◽  
Seth M Arum ◽  
Cecilia M Smith
Keyword(s):  
Vitamin D ◽  
Pulmonary Function ◽  
Lung Disease ◽  
Vitamin D Deficiency ◽  
Chronic Lung Disease ◽  
Obstructive Lung Disease ◽  
Lung Diseases ◽  
Chronic Obstructive Lung Disease ◽  
Chronic Obstructive ◽  
Chronic Lung Diseases

Vitamin D deficiency is increasingly being recognized as a prevalent problem in the general population. Patients with chronic lung diseases such as asthma, cystic fibrosis, chronic obstructive lung disease and interstitial pneumonia appear to be at increased risk for vitamin D deficiency for reasons that are not clear.Several studies indicate that vitamin D possesses a range of anti-inflammatory properties and may be involved in processes other than the previously believed functions of calcium and phosphate homeostasis. Various cytokines, cellular elements, oxidative stress and protease/antiprotease levels appear to affect lung fibroproliferation, remodelling and function, which may be influenced by vitamin D levels. Chronic lung diseases such as asthma and chronic obstructive lung disease have also been linked to vitamin D on a genetic basis. This immune and genetic influence of vitamin D may influence the pathogenesis of chronic lung diseases. A recent observational study notes a significant association between vitamin D deficiency and decreased pulmonary function tests in a large ambulatory population.The present review will examine the current literature regarding vitamin D deficiency, its prevalence in patients with chronic lung disease, vitamin D anti-inflammatory properties and the role of vitamin D in pulmonary function.

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.

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