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 Regulation of nuclear–cytoplasmic shuttling and function of Family with sequence similarity 13, member A (Fam13a), by B56-containing PP2As and Akt

2015 ◽  
Vol 26 (6) ◽  
pp. 1160-1173 ◽  
Author(s):  
Zhigang Jin ◽  
Jin Wei Chung ◽  
Wenyan Mei ◽  
Stefan Strack ◽  
Chunyan He ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Wnt Signaling ◽  
Lung Diseases ◽  
Human Lung ◽  
Sequence Similarity ◽  
Association Studies ◽  
Human Lung Cancer ◽  
Chronic Obstructive ◽  
Genome Wide Association Studies ◽  
Obstructive Pulmonary Disease

Recent genome-wide association studies reveal that the FAM13A gene is associated with human lung function and a variety of lung diseases, including chronic obstructive pulmonary disease, asthma, lung cancer, and pulmonary fibrosis. The biological functions of Fam13a, however, have not been studied. In an effort to identify novel substrates of B56-containing PP2As, we found that B56-containing PP2As and Akt act antagonistically to control reversible phosphorylation of Fam13a on Ser-322. We show that Ser-322 phosphorylation acts as a molecular switch to control the subcellular distribution of Fam13a. Fam13a shuttles between the nucleus and cytoplasm. When Ser-322 is phosphorylated by Akt, the binding between Fam13a and 14-3-3 is enhanced, leading to cytoplasmic sequestration of Fam13a. B56-containing PP2As dephosphorylate phospho–Ser-322 and promote nuclear localization of Fam13a. We generated Fam13a-knockout mice. Fam13a-mutant mice are viable and healthy, indicating that Fam13a is dispensable for embryonic development and physiological functions in adult animals. Intriguingly, Fam13a has the ability to activate the Wnt pathway. Although Wnt signaling remains largely normal in Fam13a-knockout lungs, depletion of Fam13a in human lung cancer cells causes an obvious reduction in Wnt signaling activity. Our work provides important clues to elucidating the mechanism by which Fam13a may contribute to human lung diseases.

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 Shared epithelial pathways to lung repair and disease

2017 ◽  
Vol 26 (144) ◽  
pp. 170048 ◽  
Author(s):  
Magda Spella ◽  
Ioannis Lilis ◽  
Georgios T. Stathopoulos
Keyword(s):  
Epithelial Cells ◽  
Lung Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Lung Epithelial Cells ◽  
Chronic Obstructive ◽  
Lung Repair ◽  
Chronic Lung Diseases ◽  
Lung Epithelial ◽  
Lung Regeneration

Chronic lung diseases present tremendous health burdens and share a common pathobiology of dysfunctional epithelial repair. Lung adenocarcinoma, the leading cancer killer worldwide, is caused mainly by chemical carcinogens of tobacco smoke that induce mutations in pulmonary epithelial cells leading to uncontrolled epithelial proliferation. Lung epithelial cells that possess the capacity for self-renewal and regeneration of other lung cell types are believed to underlie the pathobiology of chronic obstructive, fibrotic and neoplastic lung disorders. However, the understanding of lung epithelial progenitor cell hierarchy and turnover is incomplete and a comprehensive model of the cellular and transcriptional events that underlie lung regeneration and carcinogenesis is missing. The mapping of these processes is extremely important, since their modulation would potentially allow effective cure and/or prevention of chronic lung diseases. In this review we describe current knowledge on cellular and molecular pathways at play during lung repair and carcinogenesis and summarise the critical lung cell populations with regenerative and cancerous potential.

scholarly journals Exhaled Air Analysis in Patients with Different Lung Diseases Using Artificial Odour Sensors

2009 ◽  
Vol 63 (4-5) ◽  
pp. 210-213
Author(s):  
Immanuels Taivans ◽  
Normunds Jurka ◽  
Līga Balode ◽  
Māris Bukovskis ◽  
Uldis Kopeika ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Diseases ◽  
Clinical Medicine ◽  
Chronic Obstructive ◽  
Exhaled Breath ◽  
Air Pollution Control ◽  
Air Analysis ◽  
Artificial Nose ◽  
Chronic Lung Diseases ◽  
Exhaled Air

Exhaled Air Analysis in Patients with Different Lung Diseases Using Artificial Odour Sensors Sniffing breath to diagnose a disease has been practiced by doctors since ancient times. Nowadays, electronic noses are successfully used in the food, textile and perfume industry as well as for air pollution control. The aim of this study was to test whether exhaled breath analysed by an artificial nose could identify and discriminate between different lung diseases. A total of 76 individuals were tested: 25 bronchial asthma, 19 lung cancer, 10 pneumonia, 6 chronic obstructive pulmonary disease (COPD) patients and 16 healthy volunteers. Exhaled air was collected in plastic bags and immediately analysed using an electronic nose instrument (9185, Nordic Sensors AB) containing 14 different odour sensors. Multifactor logistic regression analysis was used to determine correlation between the amplitudes of sensor responses and the clinical diagnoses of patients and to calculate sensitivity and specificity of the method for each diagnosis. For diagnostics of asthma the sensitivity was found to be 84% and specificity — 86%. For lung cancer, the sensitivity was 74% and specificity, 95%; for pneumonia 90% and 98%, but for COPD, 33% and 97%, respectively. We conclude that an artificial nose is able to discriminate among different lung diseases with sufficiently good accuracy. This method may be further developed to implement it in clinical medicine for express diagnostics of acute and chronic lung diseases.

scholarly journals The Role of Lycopene in Chronic Lung Diseases

2021 ◽  
Author(s):  
Emilio Balbuena ◽  
Junrui Cheng ◽  
Abdulkerim Eroglu
Keyword(s):  
Lung Cancer ◽  
Lung Diseases ◽  
Protective Role ◽  
In Vivo Studies ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Bell Peppers

Lycopene, a naturally occurring non-provitamin A carotenoid pigment, is responsible for the red to pink colors in tomato, watermelon, red bell peppers, and pink guava. There are many health benefits attributed to lycopene including but not limited to its antioxidant activity. According to the American Lung Association’s State of Lung Cancer, lung cancer is still the leading cause of cancer death in the United States. Other chronic lung diseases such as asthma, emphysema, and chronic obstructive pulmonary disease are high prevalence. This chapter summarizes lycopene’s protective role against lung diseases in both in vitro and in vivo studies. While it has been demonstrated that circulating lycopene can be used as a biomarker for several lung diseases, further studies are warranted to establish that. We aim to provide insights into how lycopene can remedy for lung diseases, including lung cancer.

scholarly journals The roles of exosomal miRNAs and lncRNAs in lung diseases

2019 ◽  
Vol 4 (1) ◽  
Author(s):  
Yang Li ◽  
Zhengrong Yin ◽  
Jinshuo Fan ◽  
Siyu Zhang ◽  
Weibing Yang
Keyword(s):  
Lung Cancer ◽  
Information Exchange ◽  
Lung Diseases ◽  
Cell Communication ◽  
Diagnostic Methods ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Diagnostic Biomarkers ◽  
Exosomal Mirnas ◽  
New Ideas

Abstract An increasing number of studies have reported that exosomes released from various cells can serve as mediators of information exchange between different cells. With further exploration of exosome content, a more accurate molecular mechanism involved in the process of cell-to-cell communication has been revealed; specifically, microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are shuttled by exosomes. In addition, exosomal miRNAs and lncRNAs may play vital roles in the pathogenesis of several respiratory diseases, such as chronic obstructive pulmonary disease (COPD), lung cancer, and asthma. Consequently, exosomal miRNAs and lncRNAs show promise as diagnostic biomarkers and therapeutic targets in several lung diseases. This review will summarize recent knowledge about the roles of exosomal miRNAs and lncRNAs in lung diseases, which has shed light on the discovery of novel diagnostic methods and treatments for these disorders. Because there is almost no published literature about exosomal lncRNAs in COPD, asthma, interstitial lung disease, or tuberculosis, we summarize the roles of exosomal lncRNAs only in lung cancer in the second section. This may inspire some new ideas for researchers who are interested in whether lncRNAs shuttled by exosomes may play roles in other 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.

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