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Airway remodelling

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https://www.readbyqxmd.com/read/28076322/aeroallergen-der-p-2-promotes-motility-of-human-non-small-cell-lung-cancer-cells-via-toll-like-receptor-mediated-up-regulation-of-urokinase-type-plasminogen-activator-and-integrin-focal-adhesion-kinase-signaling
#1
Chun-Hsiang Lin, Hui-Han Lin, Cheng-Yi Kuo, Shao-Hsuan Kao
House dust mite (HDM) allergens are one of the major causes leading to respiratory hypersensitiveness and airway remodeling. Here we hypothesized that a major HDM allergen Der p 2 could increase cell motility and invasiveness of non-small cell lung cancer (NSCLC) cells. Our results showed that low dose (1 and 3 μg/mL) recombinant Der p 2 protein (DP2) enhanced the migration and invasiveness of human NSCLC cell A549, H1299 and CL1-5, but nonsignificantly altered their growth. Further investigation revealed that integrin αV level was increased and its downstream signaling including focal adhesion kinase (FAK) and paxillin were activated in A549 cells exposed to DP2...
January 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/28073835/mechanosensitive-transient-receptor-potential-vanilloid-4-regulates-dermatophagoides-farinae-induced-airway-remodeling-via-2-distinct-pathways-modulating-matrix-synthesis-and-degradation
#2
Farai Gombedza, Vinay Kondeti, Nosayba Al-Azzam, Stephanie Koppes, Ernest Duah, Prachi Patil, Madison Hexter, Daniel Phillips, Charles K Thodeti, Sailaja Paruchuri
Contributions of mechanical signals to airway remodeling during asthma are poorly understood. Transient receptor potential vanilloid 4 (TRPV4), a mechanosensitive ion channel, has been implicated in cardiac and pulmonary fibrosis; however, its role in asthma remains elusive. Employing a Dermatophagoides farinae-induced asthma model, we report here that TRPV4 knockout mice were protected from D. farinae-induced airway remodeling. Furthermore, lung fibroblasts that were isolated from TRPV4 knockout mice showed diminished differentiation potential compared with wild-type mice...
January 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28066584/overexpression-of-farnesoid-x-receptor-in-small-airways-contributes-to-epithelial-to-mesenchymal-transition-and-cox-2-expression-in-chronic-obstructive-pulmonary-disease
#3
Bi Chen, Wen-Jie You, Shan Xue, Hui Qin, Xu-Ji Zhao, Miao Zhang, Xue-Qing Liu, Shu-Yang Zhu, Han-Dong Jiang
BACKGROUND: Epithelial-mesenchymal transition (EMT) and cyclooxygenase-2 (COX-2) contribute to airway remodelling and inflammation in chronic obstructive pulmonary disease (COPD). Recent data suggest that the farnesoid X receptor (FXR), a nuclear receptor traditionally considered as bile acid-activated receptor, is also expressed in non-classical bile acids target tissues with novel functions beyond regulating bile acid homeostasis. This study aimed to investigate the potential role of FXR in the development of COPD, as well as factors that affect FXR expression...
November 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28063043/subcutaneous-and-sublingual-immunotherapy-in-a-mouse-model-of-allergic-asthma
#4
Laura Hesse, Martijn C Nawijn
Allergic asthma, caused by inhaled allergens such as house dust mite or grass pollen, is characterized by reversible airway obstruction, associated with an eosinophilic inflammation of the airways, as well as airway hyper responsiveness and remodeling. The inhaled allergens trigger a type-2 inflammatory response with involvement of innate lymphoid cells (ILC2) and Th2 cells, resulting in high production of immunoglobulin E (IgE) antibodies. Consequently, renewed allergen exposure results in a classic allergic response with a distinct early and late phase, both resulting in bronchoconstriction and shortness of breath...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28062484/heterogeneity-of-airway-dimensions-in-humans-a-critical-determinant-of-lung-function-in-asthmatics-and-non-asthmatics
#5
Christopher D Pascoe, Chun Y Seow, Tillie-Louise Hackett, Peter D Paré, Graham M Donovan
Airway remodeling, a key feature of asthma, alters every layer of the airway wall but most strikingly the airway smooth muscle (ASM) layer. Airway remodeling in asthmatics contributes to fixed airflow obstruction and can amplify airway narrowing caused by ASM activation. Previous modeling studies have shown that the increase in ASM mass has the largest effect on increasing maximal airway narrowing. Simulated heterogeneity in the dimensions and properties of the airway wall can further amplify airway narrowing...
January 6, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28062322/mir-23b-controls-tgf-%C3%AE-1-induced-airway-smooth-muscle-cell-proliferation-via-direct-targeting-of-smad3
#6
Ming Chen, Jianting Shi, Wei Zhang, Linjie Huang, Xiaoling Lin, Zhiqiang Lv, Wei Zhang, Ruiyun Liang, Shanping Jiang
BACKGROUND: MicroRNAs are small yet versatile gene tuners that regulate a variety of cellular processes, including cell growth and proliferation. Here we report that miR-23b inhibited airway smooth muscle cells (ASMCs) proliferation through directly targeting of Smad3. METHODS: We obtained ASMCs by laser capture microdissection of normal and asthmatic mice lung tissues. Mice ASMCs were cultured and induced by TGF-β1. The implication between TGF-β1 and miR-23b in ASMCs were detected by RT-PCR...
January 3, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28056993/effect-of-active-vitamin-d3-on-vegf-induced-adam33-expression-and-proliferation-in-human-airway-smooth-muscle-cells-implications-for-asthma-treatment
#7
Sung-Ho Kim, Qing-Mei Pei, Ping Jiang, Min Yang, Xue-Jiao Qian, Jiang-Bo Liu
BACKGROUND: Asthma is a chronic respiratory disease characterized by reversible airway obstruction with persistent airway inflammation and airway remodeling, which is associated with increased airway smooth muscle (ASM) mass. Vascular endothelial growth factor (VEGF) has been implicated in inflammatory and airway blood vessel remodeling in asthma. Recent evidence indicates that a deficiency of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) may influence asthma pathogenesis. A disintegrin and metalloproteinase (ADAM)33 has been identified as playing a role in the pathophysiology of asthma...
January 5, 2017: Respiratory Research
https://www.readbyqxmd.com/read/28042341/anti-angiogenic-nanotherapy-inhibits-airway-remodeling-and-hyper-responsiveness-of-dust-mite-triggered-asthma-in-the-brown-norway-rat
#8
Gregory M Lanza, John Jenkins, Anne H Schmieder, Aigul Moldobaeva, Grace Cui, Huiying Zhang, Xiaoxia Yang, Qiong Zhong, Jochen Keupp, Ismail Sergin, Krishna S Paranandi, Lindsey Eldridge, John S Allen, Todd Williams, Michael J Scott, Babak Razani, Elizabeth M Wagner
Although angiogenesis is a hallmark feature of asthmatic inflammatory responses, therapeutic anti-angiogenesis interventions have received little attention. Objective: Assess the effectiveness of anti-angiogenic Sn2 lipase-labile prodrugs delivered via αvβ3-micellar nanotherapy to suppress microvascular expansion, bronchial remodeling, and airway hyper-responsiveness in Brown Norway rats exposed to serial house dust mite (HDM) inhalation challenges. Results: Anti-neovascular effectiveness of αvβ3-mixed micelles incorporating docetaxel-prodrug (Dxtl-PD) or fumagillin-prodrug (Fum-PD) were shown to robustly suppress neovascular expansion (p<0...
2017: Theranostics
https://www.readbyqxmd.com/read/28040290/obstructive-sleep-and-atrial-fibrillation-pathophysiological-mechanisms-and-therapeutic-implications
#9
REVIEW
Christos A Goudis, Dimitrios G Ketikoglou
Atrial fibrillation (AF) is the commonest arrhythmia in clinical practice and is associated with increased cardiovascular morbidity and mortality. Obstructive sleep apnea (OSA), a common breathing disorder, is an independent risk factor for AF. Several pathophysiological mechanisms, including apnea-induced hypoxia, intrathoracic pressure shifts, sympathovagal imbalance, atrial remodeling, oxidative stress, inflammation and neurohumoral activation have been implicated in the occurrence of AF in OSA patients...
December 22, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/28034747/inhibition-of-trpc3-downregulates-airway-hyperresponsiveness-remodeling-of-ova-sensitized-mouse
#10
Lingwei Wang, Jie Li, Jian Zhang, Qi He, Xuanwen Weng, Minjie Guan, Chen Qiu
Airway hyperresponsiveness (AHR), airway remodeling and inflammation are the fundamental pathological alterations that occur in asthma. Transient receptor potential canonical 3 (TRPC3) has been implicated in diverse functions of airway smooth muscle cells (ASMCs) in asthma. However, the underlying mechanisms remain incompletely understood. We investigated the mRNA and protein expression of TRPC3 in ASMCs from normal and OVA-sensitized mouse. And the effects of inhibition or knockdown of TRPC3 with Ethyl-1- (4- (2,3,3-trichloroacrylamide) phenyl) -5 - (trifluoromethyl) -1H -pyrazole -4-carboxylate (Pyr3) and lentiviral shRNA on OVA-sensitized mouse AHR, airway remodeling, circulating inflammatory cytokines, cell proliferation and migration...
December 26, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28030368/sphingolipids-ormdl3-and-asthma-what-is-the-evidence
#11
Tilla S Worgall
PURPOSE OF REVIEW: Genome-wide association studies identified ORMDL3, a protein of the endoplasmic reticulum, as a significant asthma risk factor. ORMDL3 is one of three ORMDL proteins that integrate multiple signals to maintain sphingolipid homeostasis. Studies that investigated potential mechanisms for how increased ORMDL3 might affect asthma are summarized. RECENT FINDINGS: Investigations focused on decreased sphingolipid synthesis and on the unfolded protein response because ORMDL3 had been implicated in both...
December 24, 2016: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28025669/bronchoconstriction-induces-structural-and-functional-airway-alterations-in-non-sensitized-rats
#12
Mehdi Eslami-Behroozi, Saeed Pazhoohan, Ehsan Aref, Leila Zare, Mohammad Javan, Sohrab Hajizadeh, Mohammad Reza Raoufy
The impact of mechanical forces on pathogenesis of airway remodeling and the functional consequences in asthma remains to be fully established. In the present study, we investigated the effect of repeated bronchoconstriction induced by methacholine (MCh) on airway remodeling and airway hyperresponsiveness (AHR) in rats with or without sensitization to an external allergen. We provide evidence that repeated bronchoconstriction, using MCh, alone induces airway inflammation and remodeling as well as AHR in non-allergen-sensitized rats...
December 26, 2016: Lung
https://www.readbyqxmd.com/read/28002338/sputum-pentraxin-3-as-a-candidate-to-assess-airway-inflammation-and-remodeling-in-childhood-asthma
#13
Min Jung Kim, Hee Seon Lee, In Suk Sol, Mi Na Kim, Jung Yeon Hong, Kyung Eun Lee, Yoon Hee Kim, Kyung Won Kim, Myung Hyun Sohn, Kyu-Earn Kim
Pentraxin 3 (PTX3) is a soluble pattern recognition receptor and an acute-phase protein. It has gained attention as a new biomarker reflecting tissue inflammation and damage in a variety of diseases. Aim of this study is to investigate the role of PTX3 in childhood asthma.In total, 260 children (140 patients with asthma and 120 controls) were enrolled. PTX3 levels were measured in sputum supernatants using enzyme-linked immunosorbent assay test. We performed spirometry and methacholine challenge tests and measured the total eosinophil count and the serum levels of total IgE and eosinophil cationic protein (ECP) in all subjects...
December 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27986325/effects-of-transient-receptor-potential-canonical-1-trpc1-on-the-mechanical-stretch-induced-expression-of-airway-remodeling-associated-factors-in-human-bronchial-epithelioid-cells
#14
Qian Yu, Minchao Li
Research has shown that mechanical stress stimulation can cause airway remodeling. We investigate the effects of mechanical stretch on the expression of the airway remodeling-associated factors interleukin-13 (IL-13) and matrix metalloprotein-9 (MMP-9) and signaling pathways in human bronchial epithelioid (16HBE) cells under mechanical stretch. A Flexcell FX-4000 Tension System with a flexible substrate was applied to stretch 16HBE cells at a 15% elongation amplitude and 1Hz frequency, with stretching for 0...
January 25, 2017: Journal of Biomechanics
https://www.readbyqxmd.com/read/27982503/t-cells-promote-bronchial-epithelial-cells-secretion-of-matrix-metalloproteinase-9-via-a-c-c-chemokine-receptor-type-2-pathway-implications-for-chronic-lung-allograft-dysfunction
#15
M Pain, P-J Royer, J Loy, A Girardeau, A Tissot, P Lacoste, A Roux, M Reynaud-Gaubert, R Kessler, S Mussot, C Dromer, O Brugière, J-F Mornex, R Guillemain, M Dahan, C Knoop, K Botturi, C Pison, R Danger, S Brouard, A Magnan
Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation (LT). CLAD manifests as Bronchiolitis Obliterans Syndrome (BOS) or Restrictive Allograft Syndrome (RAS). Alloimmune reactions and epithelial-to-mesenchymal transition have been suggested in BOS. However, little is known regarding the role of allogenicity on epithelial cell differentiation. Primary human bronchial epithelial cells (BEC) were treated with activated T cells in the presence or absence of TGF-β...
December 16, 2016: American Journal of Transplantation
https://www.readbyqxmd.com/read/27982078/a-tnfrsf14-fc%C3%A9-ri-mast-cell-pathway-contributes-to-development-of-multiple-features-of-asthma-pathology-in-mice
#16
Riccardo Sibilano, Nicolas Gaudenzio, Marianne K DeGorter, Laurent L Reber, Joseph D Hernandez, Philipp M Starkl, Oliwia W Zurek, Mindy Tsai, Sonja Zahner, Stephen B Montgomery, Axel Roers, Mitchell Kronenberg, Mang Yu, Stephen J Galli
Asthma has multiple features, including airway hyperreactivity, inflammation and remodelling. The TNF superfamily member TNFSF14 (LIGHT), via interactions with the receptor TNFRSF14 (HVEM), can support TH2 cell generation and longevity and promote airway remodelling in mouse models of asthma, but the mechanisms by which TNFSF14 functions in this setting are incompletely understood. Here we find that mouse and human mast cells (MCs) express TNFRSF14 and that TNFSF14:TNFRSF14 interactions can enhance IgE-mediated MC signalling and mediator production...
December 16, 2016: Nature Communications
https://www.readbyqxmd.com/read/27979013/pivotal-efficacy-trials-of-inhaled-corticosteroids-in-asthma
#17
Ronina A Covar
BACKGROUND: Inhaled corticosteroids (ICSs) are the mainstay of daily controller treatment for persistent and uncontrolled asthma. However, many clinicians are wary of ICSs because of safety concerns. Clinicians need to know the underlying efficacy data that support the use of ICSs to weigh efficacy against safety. OBJECTIVE: To discuss efficacy data from pivotal trials to aid clinicians in their decisions to use ICSs. METHODS: Key efficacy studies were selected to augment discussion...
December 2016: Annals of Allergy, Asthma & Immunology
https://www.readbyqxmd.com/read/27974233/increased-deposition-of-glycosaminoglycans-and-altered-structure-of-heparan-sulfate-in-idiopathic-pulmonary-fibrosis
#18
Gunilla Westergren-Thorsson, Ulf Hedström, Annika Nybom, Emil Tykesson, Emma Åhrman, Marie Hornfelt, Marco Maccarana, Toin H van Kuppevelt, Göran Dellgren, Marie Wildt, Xiao-Hong Zhou, Leif Eriksson, Leif Bjermer, Oskar Hallgren
Idiopathic pulmonary fibrosis (IPF) is characterized by aberrant deposition of extracellular matrix (ECM) constituents, including glycosaminoglycans (GAGs), that may play a role in remodelling processes by influencing critical mediators such as growth factors. We hypothesize that GAGs may be altered in IPF and that this contribute to create a pro-fibrotic environment. The aim of this study was therefore to examine the fine structure of heparan sulfate (HS), chondroitin/dermatan sulfate (CS/DS) and hyaluronan (HA) in lung samples from IPF patients and from control subjects...
December 11, 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27956356/a-standardized-methanol-extract-of-eclipta-prostrata-l-l-asteraceae-reduces-bronchial-hyperresponsiveness-and-production-of-th2-cytokines-in-a-murine-model-of-asthma
#19
Lucas Junqueira de Freitas Morel, Bruna Cestari de Azevedo, Fábio Carmona, Silvia Helena Taleb Contini, Aristônio Magalhães Teles, Fernando Silva Ramalho, Bianca Waléria Bertoni, Suzelei de Castro França, Marcos de Carvalho Borges, Ana Maria Soares Pereira
ETHNOPHARMACOLOGICAL RELEVANCE: Eclipta prostrata (L.) L. (Asteraceae) has been used in Brazilian traditional medicine to treat asthma and other respiratory illnesses. AIMS OF THE STUDY: To investigate the effects of different doses of a standardized extract of E. prostrata using a murine model of allergen induced asthma. MATERIALS AND METHODS: Balb/c mice were sensitized twice with ovalbumin (OVA) administered intraperitoneally and challenged over four alternate days with nasal instillations of OVA solution...
December 9, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27942595/single-cell-rna-sequencing-identifies-diverse-roles-of-epithelial-cells-in-idiopathic-pulmonary-fibrosis
#20
Yan Xu, Takako Mizuno, Anusha Sridharan, Yina Du, Minzhe Guo, Jie Tang, Kathryn A Wikenheiser-Brokamp, Anne-Karina T Perl, Vincent A Funari, Jason J Gokey, Barry R Stripp, Jeffrey A Whitsett
Idiopathic pulmonary fibrosis (IPF) is a lethal interstitial lung disease characterized by airway remodeling, inflammation, alveolar destruction, and fibrosis. We utilized single-cell RNA sequencing (scRNA-seq) to identify epithelial cell types and associated biological processes involved in the pathogenesis of IPF. Transcriptomic analysis of normal human lung epithelial cells defined gene expression patterns associated with highly differentiated alveolar type 2 (AT2) cells, indicated by enrichment of RNAs critical for surfactant homeostasis...
December 8, 2016: JCI Insight
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