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https://www.readbyqxmd.com/read/28424075/computational-modeling-of-airway-instability-and-collapse-in-tracheomalacia
#1
Scott J Hollister, Maximilian P Hollister, Sebastian K Hollister
BACKGROUND: Tracheomalacia (TM) is a condition of excessive tracheal collapse during exhalation. Both acquired and congenital forms of TM are believed to result from morphological changes in cartilaginous, fibrous and/or smooth muscle tissues reducing airway mechanical properties to a degree that precipitates collapse. However, neither the specific amount of mechanical property reduction nor the malacic segment lengths leading to life threatening airway collapse in TM are known. Furthermore, the specific mechanism of collapse is still debated...
April 19, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28421197/ginsenoside-rg1-ameliorates-cigarette-smoke-induced-airway-fibrosis-by-suppressing-the-tgf-%C3%AE-1-smad-pathway-in-vivo-and-in-vitro
#2
Sibin Guan, Qian Liu, Fengfeng Han, Wen Gu, Lin Song, Yue Zhang, Xuejun Guo, Weiguo Xu
Small airway fibrosis is a key pathological process accompanying chronic obstructive pulmonary disease (COPD) and includes fibroblast/myofibroblast transdifferentiation and excessive extracellular matrix deposition. Ginsenoside Rg1, one of the main active ingredients of Panax ginseng, has been shown to exert an antifibrotic effect in many tissues. However, little is known about the underlying mechanism and whether ginsenoside Rg1 can exert an effect on small airway fibrosis. We investigated the anti-small airway fibrosis effects of ginsenoside Rg1 in human embryonic lung fibroblasts and in COPD rats...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28414142/doxofylline-does-not-increase-formoterol-induced-camp-nor-mkp-1-expression-in-asm-cells-resulting-in-lack-of-anti-inflammatory-effect
#3
Brijeshkumar S Patel, Michael J Kugel, Gina Baehring, Alaina J Ammit
The xanthine doxofylline has been examined in clinical trials and shown to have efficacy and greater tolerability than theophylline in asthma and chronic obstructive pulmonary disease. The 'novofylline' doxofylline has demonstrated bronchodilatory and anti-inflammatory actions in in vivo and ex vivo experimental models of respiratory disease. However, there are limited studies in vitro. We address this herein and examine whether doxofylline has anti-inflammatory impact on primary cultures of airway smooth muscle (ASM) cells...
April 13, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28413486/cigarette-smoke-extract-promotes-proliferation-of-airway-smooth-muscle-cells-through-suppressing-c-ebp-%C3%AE-expression
#4
Pin Guan, Wentao Cai, Huapeng Yu, Zhiyong Wu, Wei Li, Jie Wu, Juan Chen, Guangqiu Feng
Cigarette smoke has been considered a major contributor to the pathogenesis of chronic obstructive pulmonary disease (COPD). In COPD patients, the airway smooth muscle layer has been observed to be markedly thickened and the proliferation of airway smooth muscle cells (ASMCs) was therefore used by the present study as a model to assess the impact of cigarette smoke extract (CSE). ASMCs were exposed to various concentrations of CSE and the proliferation of the cells was analyzed by an MTT assay. Furthermore, the expression levels of calreticulin and CCAAT/enhancer-binding protein alpha (C/EBP-α) in CSE-stimulated ASMCs were determined by polymerase chain reaction and western blot analyses...
April 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28406326/umeclidinium-for-the-treatment-of-uncontrolled-asthma
#5
Matteo Ferrando, Diego Bagnasco, Fulvio Braido, Ilaria Baiardini, Giovanni Passalacqua, Francesca Puggioni, Gilda Varricchi, Giorgio Walter Canonica
Smooth muscle cell contraction in the airways is the principal therapeutic target in asthmatic subjects and its insufficient treatment is often a cause of uncontrolled disease. For this reason, research has focused on targeting smooth muscle activity with anticholinergic agents, including umeclidinium. Areas Covered: This review highlights the potential application of umeclidinium, a long acting muscarinic antagonist, as a novel therapeutic approach for patients with severe uncontrolled asthma, despite maximal therapy...
April 13, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/28402030/cyclic-peptide-crretawac-attenuates-fibronectin-induced-cytokine-secretion-of-human-airway-smooth-muscle-cells-by-inhibiting-fak-and-p38-mapk
#6
Mengdi Chu, Jiani Ji, Wenhao Cao, Huojun Zhang, Dan Meng, Bangruan Xie, Shuyun Xu
α5β1 integrin is highly expressed in airway smooth muscle cells and mediate the adhesion of airway smooth muscle cells to fibronectin to regulate airway remodelling in asthma. This study aimed to investigate the effects of synthetic cyclic peptide *CRRETAWAC* on fibronectin-induced cytokine secretion of airway smooth muscle cells and the underlying mechanism. Human airway smooth muscle cells were isolated and treated with fibronectin, IL-13, *CRRETAWAC* peptide, α5β1 integrin-blocking antibody, FAK inhibitor or p38 MAPK inhibitor...
April 12, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28397820/bitter-taste-receptor-agonists-mitigate-features-of-allergic-asthma-in-mice
#7
Pawan Sharma, Roslyn Yi, Ajay P Nayak, Nadan Wang, Francesca Tang, Morgan J Knight, Shi Pan, Brian Oliver, Deepak A Deshpande
Asthma is characterized by airway inflammation, mucus secretion, remodeling and hyperresponsiveness (AHR). Recent research has established the bronchodilatory effect of bitter taste receptor (TAS2R) agonists in various models. Comprehensive pre-clinical studies aimed at establishing effectiveness of TAS2R agonists in disease models are lacking. Here we aimed to determine the effect of TAS2R agonists on features of asthma. Further, we elucidated a mechanism by which TAS2R agonists mitigate features of asthma...
April 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28393245/knockdown-of-fstl1-inhibits-pdgf%C3%A2-bb%C3%A2-induced-human-airway-smooth-muscle-cell-proliferation-and-migration
#8
Yuelin Deng, Yao Zhang, Huajie Wu, Zhaoling Shi, Xin Sun
Abnormal proliferation and migration of airway smooth muscle (ASM) cells serve roles in airway remodeling, and contribute to airway hyper‑responsiveness. Follistatin‑like protein 1 (FSTL1) is a secreted glycoprotein that belongs to the follistatin family of proteins. It was reported that in the lungs of patients suffering from severe asthma, FSTL1 is highly expressed by macrophages. However, the role of FSTL1 in ASM cell proliferation and migration remains unknown. The present study aimed to investigate the role of FSTL1 in cell proliferation and migration mediated by platelet‑derived growth factor subunit B (PDGF‑BB) in human ASM cells...
April 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28390425/the-roles-and-regulation-of-the-actin-cytoskeleton-intermediate-filaments-and-microtubules-in-smooth-muscle-cell-migration
#9
REVIEW
Dale D Tang, Brennan D Gerlach
Smooth muscle cell migration has been implicated in the development of respiratory and cardiovascular systems; and airway/vascular remodeling. Cell migration is a polarized cellular process involving a protrusive cell front and a retracting trailing rear. There are three cytoskeletal systems in mammalian cells: the actin cytoskeleton, the intermediate filament network, and microtubules; all of which regulate all or part of the migrated process. The dynamic actin cytoskeleton spatially and temporally regulates protrusion, adhesions, contraction, and retraction from the cell front to the rear...
April 8, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28387977/ex-vivo-analysis-of-the-contribution-of-fgf10-cells-to-airway-smooth-muscle-cell-formation-during-early-lung-development
#10
Elie El Agha, Vahid Kheirollahi, Alena Moiseenko, Werner Seeger, Saverio Bellusci
BACKGROUND: Airway smooth muscle cells (ASMCs) have been widely studied during embryonic lung development. These cells have been shown to control epithelial bifurcation during branching morphogenesis. Fibroblast growth factor 10-positive (FGF10(+) ) cells, originally residing in the submesothelial mesenchyme, contribute to ASMC formation in the distal lung. The reported work aims at monitoring the response of FGF10(+) progenitors and differentiated ASMCs to growth factor treatment in real time using lineage tracing in the background of an air-liquid interface culture system...
April 7, 2017: Developmental Dynamics: An Official Publication of the American Association of Anatomists
https://www.readbyqxmd.com/read/28385814/tnf%C3%AE-enhances-force-generation-in-airway-smooth-muscle
#11
Murat Dogan, Young-Soo Han, Philippe F Delmotte, Gary C Sieck
Airway inflammation is a hallmark of asthma triggering airway smooth muscle (ASM) hyperreactivity and airway remodeling. TNFα increases both agonist-induced cytosolic Ca(2+) concentration and force in ASM. The effects of TNFα on ASM force may also be due to an increase in Ca(2+) sensitivity, cytoskeletal remodeling and/or changes in contractile protein content. We hypothesized that 24-h exposure TNFα increases ASM force by changing actin and myosin heavy chain (MyHC) content and/or polymerization. Porcine ASM strips were permeabilized with 10% Triton X-100, and force was measured in response to increasing concentrations of Ca(2+) (pCa 9...
April 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28385073/mentha-arvensis-essential-oil-suppressed-airway-changes-induced-by-histamine-and-ovalbumin-in-experimental-animals
#12
Shilpa Sharma, Vijaykumar P Rasal, Paragouda A Patil, Rajesh K Joshi
The present investigation aimed to evaluate the activity of the essential oil of Mentha arvensis L. on exogenously induced bronchoconstriction in experimental animals. The anti-asthmatic effect of M. arvensis essential oil (MAEO) was studied using histamine aerosol-induced bronchoconstriction in guinea pigs and ovalbumin (OVA) sensitised albino mice. Treatment with M. arvensis oil significantly (p < 0.001) increased the time of preconvulsive dyspnoea in histamine-induced guinea pigs. Oral treatment of MAEO significantly (p < 0...
April 7, 2017: Natural Product Research
https://www.readbyqxmd.com/read/28381600/increased-neutrophil-gelatinase-associated-lipocalin-ngal-promotes-airway-remodelling-in-chronic-obstructive-pulmonary-disease
#13
Yujie Wang, Man Jia, Xiaoyi Yan, Limin Cao, Peter J Barnes, Ian M Adcock, Mao Huang, Xin Yao
Airway remodelling is an important component of chronic obstructive pulmonary disease (COPD). Neutrophil gelatinase-associated lipocalin (NGAL) from neutrophils may drive COPD epithelial-mesenchymal transition (EMT). NGAL expression was quantified in the lungs of COPD patients and bronchoalveolar lavage fluid (BALF) of ozone-treated mice. Reticular basement membrane (RBM) thickness and E-cadherin and α-smooth muscle actin (α-SMA) expression were determined in mice airways. Effects of cigarette smoke extract (CSE) and inflammatory factors on NGAL expression in human neutrophils as well as the effects of NGAL on airway structural cells was assessed...
April 5, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28375666/glucocorticoid-receptor-chip-seq-identifies-plcd1-as-a-klf15-target-that-represses-airway-smooth-muscle-hypertrophy
#14
Sarah K Sasse, Vineela Kadiyala, Thomas Danhorn, Reynold A Panettieri, Tzu L Phang, Anthony N Gerber
Glucocorticoids exert important therapeutic effects on airway smooth muscle (ASM), yet few direct targets of glucocorticoid signaling in ASM have been definitively identified. Here, we show that the transcription factor, KLF15, is directly induced by glucocorticoids in primary human ASM and that KLF15 represses ASM hypertrophy. We integrated transcriptome data from KLF15 overexpression with genome-wide analysis of RNA Polymerase II (RNAPII) and glucocorticoid receptor (GR) occupancy (i.e. ChIP-seq) to identify PLCD1 as both a KLF15-regulated gene and a novel repressor of ASM hypertrophy...
April 4, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28370670/origin-and-characterization-of-alpha-smooth-muscle-actin-positive-cells-during-murine-lung-development
#15
Alena Moiseenko, Vahid Kheirollahi, Cho-Ming Chao, Negah Ahmadvand, Jennifer Quantius, Jochen Wilhelm, Susanne Herold, Katrin Ahlbrecht, Rory E Morty, Albert A Rizvanov, Parviz Minoo, Elie El Agha, Saverio Bellusci
ACTA2 expression identifies pulmonary airway and vascular smooth muscle cells (SMCs) as well as alveolar myofibroblasts (MYF). Mesenchymal progenitors expressing fibroblast growth factor 10 (Fgf10), Wilms tumor 1 (Wt1), or glioma-associated oncogene 1 (Gli1) contribute to SMC formation from early stages of lung development. However, their respective contribution and specificity to the SMC and/or alveolar MYF lineages remain controversial. In addition, the contribution of mesenchymal cells undergoing active WNT signaling remains unknown...
April 3, 2017: Stem Cells
https://www.readbyqxmd.com/read/28360113/directional-preference-of-airway-smooth-muscle-mass-increase-in-human-asthmatic-airways
#16
Gijs Ijpma, Alice Panariti, Anne-Marie Lauzon, James G Martin
Airway smooth muscle (ASM) orientation and morphology determine the ability of the muscle to constrict the airway. In asthma, ASM mass is increased, but it is unknown whether ASM orientation and morphology are altered as well, or whether the remodelling at the source of the mass increase is ongoing. We dissected human airway trees from asthmatic and control lungs. Stained, intact airway sections were imaged in axial projection to show ASM bundle orientation, while cross-sectional histological slides were used to assess ASM area, bundle thickness and ASM bundle to basement membrane distance...
March 30, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28356076/dexmedetomidine-s-inhibitory-effects-on-acetylcholine-release-from-cholinergic-nerves-in-guinea-pig-trachea-a-mechanism-that-accounts-for-its-clinical-benefit-during-airway-irritation
#17
Maya Mikami, Yi Zhang, Benjamin Kim, Tilla S Worgall, Harald Groeben, Charles W Emala
BACKGROUND: Airway instrumentation can evoke upper airway reflexes including bronchoconstriction and cough which can cause serious complications including airway trauma, laryngospasm or bronchospasm which may in turn lead to difficulty with ventilation and hypoxemia. These airway events are mediated in part by irritant-induced neuronal modulation of airway tone and cough responses. We investigated whether the commonly used anesthetic agents dexmedetomidine, lidocaine or remifentanil attenuated neuronal and airway smooth muscle responses in the upper airways of guinea pigs...
March 29, 2017: BMC Anesthesiology
https://www.readbyqxmd.com/read/28336814/airway-smooth-muscle-dysfunction-in-pompe-gaa-mice
#18
Allison M Keeler, Donghai Liu, Marina Zieger, Lang Xiong, Jeffrey Salemi, Karl Bellve, Barry J Byrne, David D Fuller, Ronghua ZhuGe, Mai K ElMallah
Pompe disease is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase (GAA) - an enzyme responsible for hydrolyzing lysosomal glycogen. Deficiency of GAA leads to systemic glycogen accumulation in the lysosomes of skeletal muscle, motor neurons and smooth muscle. Skeletal muscle and motor neuron pathology are known to contribute to respiratory insufficiency in Pompe disease, but the role of airway pathology has not been evaluated. Here we propose that GAA enzyme deficiency disrupts the function of the trachea and bronchi, and this lower airway pathology contributes to respiratory insufficiency in Pompe disease...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28336810/role-of-transient-receptor-potential-vanilloid-1-trpv1-in-the-modulation-of-airway-smooth-muscle-tone-and-calcium-handling
#19
Gene T Yocum, Jun Chen, Christine H Choi, Elizabeth A Townsend, Yi Zhang, Dingbang Xu, Xiao Wen Fu, Michael J Sanderson, Charles W Emala
Asthma is a common disorder characterized, in part, by airway smooth muscle (ASM) hyperresponsiveness. Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel expressed on airway nerve fibers that modulates afferent signals resulting in cough, and potentially bronchoconstriction. In the present study, the TRPV1 transcript was detected by RT-PCR in primary cultured human ASM cells, and the TRPV1 protein was detected in ASM of human trachea by immunohistochemistry. Proximity ligation assays suggest that TRPV1 is expressed in the sarcoplasmic reticulum membrane of human ASM cells in close association with sarco/endoplasmic reticulum Ca2+ ATPase 2...
March 23, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28336486/mitochondrial-dysfunction-in-airway-disease
#20
Y S Prakash, Christina M Pabelick, Gary C Sieck
There is increasing appreciation that mitochondria serve cellular functions beyond oxygen sensing and energy production. Accordingly, it has become important to explore non-canonical roles of mitochondria in normal and pathophysiological processes that influence airway structure and function in the context of diseases such as asthma and COPD. Mitochondria can sense upstream processes such as inflammation, infection, tobacco smoke and environmental insults important in these diseases, and in turn can respond to such stimuli via altered mitochondrial protein expression, structure, and resultant dysfunction...
March 21, 2017: Chest
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