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Airway remodelling

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https://www.readbyqxmd.com/read/30015827/bms%C3%A2-345541-inhibits-airway-inflammation-and-epithelial%C3%A2-mesenchymal-transition-in-airway-remodeling-of-asthmatic-mice
#1
Xiaohua Zhu, Qiugen Li, Guozhu Hu, Jun Wang, Qinghua Hu, Zhiqiang Liu, Gang Wu, Ying Zhong
The present study aimed to investigate the possible effects and regulatory mechanism of the inhibitor of nuclear factor‑κB kinase complex β subunit (IKKβ) inhibitor BMS‑345541 on airway inflammation, airway remodeling and epithelial‑mesenchymal transition (EMT) in an ovalbumin (OVA) exposure asthma model in mice. The asthma mouse model was generated by sensitization and challenge with OVA. BMS‑345541/dimethyl sulfoxide (DMSO) was administered perorally dairy in two therapeutic groups throughout the entire OVA challenge process...
July 6, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/30013476/inhibition-of-rage-attenuates-cigarette-smoke-induced-lung-epithelial-cell-damage-via-rage-mediated-nrf2-damp-signaling
#2
Hanbyeol Lee, Jooyeon Lee, Seok-Ho Hong, Irfan Rahman, Se-Ran Yang
The oxidative stress and cellular apoptosis by environmental factor including cigarette smoke induces alveolar airway remodeling leading to chronic obstructive pulmonary disease (COPD). Recently, the receptor for advanced glycan end products (RAGE) which is highly expressed in alveolar epithelium is emerging as a biomarker for COPD susceptibility or progression. However, it still remains unknown how RAGE plays a role in cigarette smoke extract (CSE)-exposed human alveolar type II epithelial cell line. Therefore, we determined the efficacy of RAGE-specific antagonist FPS-ZM1 in response to CSE-induced lung epithelial cells...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30006538/functional-and-morphological-differences-of-the-lung-upon-acute-and-chronic-ozone-exposure-in-mice
#3
Chloé Michaudel, Louis Fauconnier, Yvon Julé, Bernhard Ryffel
Environmental air pollutants including ozone cause severe lung injury and aggravate respiratory diseases such as asthma and COPD. Here we compared the effect of ozone on respiratory epithelium injury, inflammation, hyperreactivity and airway remodeling in mice upon acute (1ppm, 1 h) and chronic exposure (1.5ppm, 2 h, twice weekly for 6 weeks). Acute ozone exposure caused respiratory epithelial disruption with protein leak and neutrophil recruitment in the broncho-alveolar space, leading to lung inflammation and airway hyperresponsiveness (AHR) to methacholine...
July 13, 2018: Scientific Reports
https://www.readbyqxmd.com/read/30006481/apoptosis-signal-regulating-kinase-1-ask1-inhibition-attenuates-human-airway-smooth-muscle-growth-and-migration-in-chronic-obstructive-pulmonary-disease-copd
#4
Mathew S Eapen, Anudeep Kota, Howard Vindin, Kielan D McAlinden, Dia Xenaki, Brian G Oliver, Deepak A Deshpande, Sukhwinder Singh Sohal, Pawan Sharma
Increased airway smooth muscle (ASM) mass is observed in COPD which is correlated with disease severity and negatively impact lung function. Thus, there is clear unmet clinical need for finding new therapies which can target airway remodeling and disease progression in COPD. Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase kinase kinase  activated by various stress stimuli, including reactive oxygen species, tumor necrosis factor-α, and lipopolysaccharide and is known to regulate cell proliferation...
July 13, 2018: Clinical Science (1979-)
https://www.readbyqxmd.com/read/30001393/effect-of-progesterone-on-smad-signaling-and-tgf-%C3%AE-smad-regulated-genes-in-lung-epithelial-cells
#5
Steffen Kunzmann, Barbara Ottensmeier, Christian P Speer, Markus Fehrholz
The effect of endogenous progesterone and/or exogenous pre- or postnatal progesterone application on lung function of preterm infants is poorly defined. While prenatal progesterone substitution may prevent preterm birth, in vitro and in vivo data suggest a benefit of postnatal progesterone replacement on the incidence and severity of bronchopulmonary dysplasia (BPD). However, the molecular mechanisms responsible for progesterone's effects are undefined. Numerous factors are involved in lung development, airway inflammation, and airway remodeling: the transforming growth factor beta (TGF-β)/mothers against decapentaplegic homolog (Smad) signaling pathway and TGF-β-regulated genes, such as connective tissue growth factor (CTGF), transgelin (TAGLN), and plasminogen activator inhibitor-1 (PAI-1)...
2018: PloS One
https://www.readbyqxmd.com/read/29997053/tgf-%C3%AE-3-promotes-muc5ac-hyper-expression-by-modulating-autophagy-pathway-in-airway-epithelium
#6
Yun Zhang, Hongmei Tang, Xiefang Yuan, Qin Ran, Xiaoyun Wang, Qi Song, Lei Zhang, Yuhuan Qiu, Xing Wang
Mucus secretion accumulation in the airways may act as a contributing factor for the development of airflow limitation in severe fetal asthma patients. Accumulated evidences showed that transforming growth factor beta (TGF-β) plays a regulatory role in airway remodeling including mucus hyper-secretion in asthma. However, the detailed molecular mechanisms of TGF-β3 induced MUC5AC hyper-expression in airway epithelium remains unclear. Here, we demonstrated the pivotal roles of autophagy in regulation of MUC5AC hyper-production induced by TGF-β3 in airway epithelium...
July 8, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29983548/mechanism-of-yanghe-pingchuan-granules-treatment-for-airway-remodeling-in-asthma
#7
Ling Yu Pan, Yan Quan Han, Yong Zhong Wang, Qian Qian Chen, Ying Wu, Yuan Sun
Purpose: Yanghe Pingchuan granules (YPG), a hospital preparation developed by The First Affiliated Hospital, Anhui University of Chinese Medicine, has been used for the clinical treatment of bronchial asthma (BA) for several decades. This study aimed to explore the mechanism of action of YPG in the treatment of BA. Materials and methods: Male Sprague Dawley rats (n=60) were randomly divided into six groups (n=10 per group): control, a BA model, positive drug control (Guilong Kechuanning capsules; a proven effective treatment for BA), and model rats treated with a high, medium, or low dose of YPG...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29980277/allergic-components-of-eosinophilic-esophagitis
#8
REVIEW
Jonathan Spergel, Seema S Aceves
Eosinophilic esophagitis (EoE) is a disorder of increasing prevalence worldwide, causing clinical symptoms of vomiting, failure to thrive, and dysphagia and complications of esophageal remodeling with strictures and food impactions. Molecular profiling demonstrates EoE to be an eosinophil-predominant disorder with a TH 2 cytokine profile reminiscent of other allergic diseases, such as asthma, allergic rhinitis, and atopic dermatitis. Environmental antigens in the form of foods and aeroallergens induce eosinophil, basophil, mast cell, and T-cell infiltration...
July 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29968161/a-theoretical-model-of-inflammation-and-mechanotransduction-driven-asthmatic-airway-remodelling
#9
Michael R Hill, Christopher J Philp, Charlotte K Billington, Amanda L Tatler, Simon R Johnson, Reuben D O'Dea, Bindi S Brook
Inflammation, airway hyper-responsiveness and airway remodelling are well-established hallmarks of asthma, but their inter-relationships remain elusive. In order to obtain a better understanding of their inter-dependence, we develop a mechanochemical morphoelastic model of the airway wall accounting for local volume changes in airway smooth muscle (ASM) and extracellular matrix in response to transient inflammatory or contractile agonist challenges. We use constrained mixture theory, together with a multiplicative decomposition of growth from the elastic deformation, to model the airway wall as a nonlinear fibre-reinforced elastic cylinder...
July 2, 2018: Biomechanics and Modeling in Mechanobiology
https://www.readbyqxmd.com/read/29966667/collagen-degradation-and-formation-are-elevated-in-exacerbated-copd-compared-to-stable-disease
#10
Desiree M Schumann, Diana Leeming, Eleni Papakonstantinou, Francesco Blasi, Konstantinos Kostikas, Wim Boersma, Renaud Louis, Branislava Milenkovic, Joachim Aerts, Jannie M B Sand, Emiel F M Wouters, Gernot Rohde, Christina Prat, Antoni Torres, Tobias Welte, Michael Tamm, Morten Karsdal, Daiana Stolz
The role of the extracellular matrix (ECM) structure and remodelling of thereof in lung diseases is gaining importance. Pathology-related changes in the ECM turnover may result in deleterious changes in lung architecture leading to disease in the small airways. Here, degradation fragments of type I (C1M), type IV (α1 chain, C4M2), and type IV (α3 chain, C4Ma3) collagen, all degraded by metalloproteinases (MMPs) and the pro-form of collagen type V (PRO-C5) were investigated and associated with chronic obstructive pulmonary disease (COPD) severity and outcome...
June 29, 2018: Chest
https://www.readbyqxmd.com/read/29958800/amphiregulin-producing-pathogenic-memory-t-helper-2-cells-instruct-eosinophils-to-secrete-osteopontin-and-facilitate-airway-fibrosis
#11
Yuki Morimoto, Kiyoshi Hirahara, Masahiro Kiuchi, Tomoko Wada, Tomomi Ichikawa, Toshio Kanno, Mikiko Okano, Kota Kokubo, Atsushi Onodera, Daiju Sakurai, Yoshitaka Okamoto, Toshinori Nakayama
Memory T cells provide long-lasting protective immunity, and distinct subpopulations of memory T cells drive chronic inflammatory diseases such as asthma. Asthma is a chronic allergic inflammatory disease with airway remodeling including fibrotic changes. The immunological mechanisms that induce airway fibrotic changes remain unknown. We found that interleukin-33 (IL-33) enhanced amphiregulin production by the IL-33 receptor, ST2hi memory T helper 2 (Th2) cells. Amphiregulin-epidermal growth factor receptor (EGFR)-mediated signaling directly reprogramed eosinophils to an inflammatory state with enhanced production of osteopontin, a key profibrotic immunomodulatory protein...
June 4, 2018: Immunity
https://www.readbyqxmd.com/read/29951106/therapeutic-effects-of-kangzhi-syrup-in-a-guinea-pig-model-of-ovalbumin-induced-cough-variant-asthma
#12
Youpeng Wang, Pengyu Zhu, Jiejun Tan, Zhiwei Liu, Wanying Qu, Lujia Liu, Zhijun Li
Purpose: This study aimed to investigate the possible effects and underlying mechanisms of Kangzhi syrup on ovalbumin- (OVA-) induced cough variant asthma (CVA) in guinea pigs. Methods: All 48 guinea pigs were randomly assigned to four experimental groups: normal, OVA model with or without Kangzhi syrup (OVA and OVA + KZ), and OVA with Dexamethasone (OVA + DM). After sensitizing the guinea pigs, a cough challenge was performed by the inhalation of capsaicin. The antitussive effect, inflammatory cells, cytokines in bronchoalveolar lavage fluid (BALF) and lung tissue, and morphological changes were examined...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/29950305/the-consequence-of-matrix-dysfunction-on-lung-immunity-and-the-microbiome-in-copd
#13
Tracy Hussell, Sylvia Lui, Christopher Jagger, David Morgan, Oliver Brand
The pulmonary extracellular matrix (ECM) is a complex network of proteins which primarily defines tissue architecture and regulates various biochemical and biophysical processes. It is a dynamic system comprising two main structures (the interstitial matrix and the basement membrane) which undergo continuous, yet highly regulated, remodelling. This remodelling process is essential for tissue homeostasis and uncontrolled regulation can lead to pathological states including chronic obstructive pulmonary disease (COPD)...
June 30, 2018: European Respiratory Review: An Official Journal of the European Respiratory Society
https://www.readbyqxmd.com/read/29949788/microrna-142-inhibits-proliferation-and-promotes-apoptosis-in-airway-smooth-muscle-cells-during-airway-remodeling-in-asthmatic-rats-via-the-inhibition-of-tgf-%C3%AE-dependent-egfr-signaling-pathway
#14
Jing Wang, Hu-Shan Wang, Zhen-Bo Su
BACKGROUND/AIMS: Asthma is a heterogeneous disease characterized by chronic airway inflammation resulting from airway hyper-responsiveness to diverse stimuli. In this study, we investigated whether microRNA-142 (miR-142) expression affects proliferation and apoptosis in airway smooth muscle cells (ASMCs) during airway remodeling in asthmatic rats. METHODS: Thirty six Wistar rats were randomly classified into a control group and an model group. miR-142 mimics and inhibitors were constructed, and ASMCs were transfected using liposomes according to the following groups: blank, negative control (NC), miR-142 mimics, miR-142 inhibitors, si-TGF-β and miR-142 inhibitors + si-TGF-β...
June 27, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29943875/inflammation-dependent-and-independent-airway-remodelling-in-asthma
#15
John G Elliot, Peter B Noble, Thais Mauad, Tony R Bai, Michael J Abramson, Karen O McKay, Francis H Y Green, Alan L James
BACKGROUND AND OBJECTIVE: The pathology of asthma is characterized by airway inflammation (granulocytic (GA) or paucigranulocytic (PGA)) and remodelling of airway structures. However, the relationship between inflammatory phenotypes and remodelling is unclear. We hypothesized that some features of airway remodelling are dependent on granulocytic airway inflammation while others are not. METHODS: Post-mortem airway sections from control subjects (n = 48) and cases of asthma with (n = 51) or without (n = 29) granulocytic inflammation in the inner airway wall were studied...
June 26, 2018: Respirology: Official Journal of the Asian Pacific Society of Respirology
https://www.readbyqxmd.com/read/29940929/the-potential-of-olea-europaea-extracts-to-prevent-tgf%C3%AE-1-induced-epithelial-to-mesenchymal-transition-in-human-nasal-respiratory-epithelial-cells
#16
Rabiatul Adawiyah Razali, Nik Ahmad Hafiz Nik Ahmad Eid, Turkambigai Jayaraman, Muhammad Asyrafi Amir Hassan, Nabilah Qistina Azlan, Nur Farhana Ismail, Nur Qisya Afifah Veronica Sainik, Muhammad Dain Yazid, Yogeswaran Lokanathan, Aminuddin Bin Saim, Ruszymah Bt Hj Idrus
BACKGROUND: One of the molecular mechanisms involved in upper airway-related diseases is epithelial-to-mesenchymal transition (EMT). Olea europaea (OE) has anti-inflammatory properties and thus, great potential to prevent EMT. This study aimed to investigate the effect of OE on EMT in primary nasal human respiratory epithelial cells (RECs). METHODS: Respiratory epithelial cells were isolated and divided into four groups: control (untreated), treated with 0.05% OE (OE group), EMT induced with 5 ng/ml of transforming growth factor beta-1 (TGFβ1 group) and treated with 5 ng/ml TGFβ1 + 0...
June 26, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29940571/thymic-stromal-lymphopoietin-signaling-pathway-inhibition-attenuates-airway-inflammation-and-remodeling-in-rats-with-asthma
#17
Zhe Cheng, Xi Wang, Ling-Ling Dai, Liu-Qun Jia, Xiao-Gang Jing, Ying Liu, Huan Wang, Peng-Fei Li, Lin An, Meng Liu
BACKGROUND/AIMS: Thymic stromal lymphopoietin (TSLP) is a cytokine that plays diverse roles in the regulation of immune responses. However, a detailed understanding of the TSLP signaling pathway in asthma remains elusive. In this study, we aimed to investigate the role of the TSLP signaling pathway in asthma and its effect on airway inflammation and remodeling. METHODS: Forty Sprague Dawley (SD) rats were evenly classified into control, asthma, IgG2a mAb and anti-TSLP mAb groups...
June 21, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29923060/therapeutic-effects-of-obeticholic-acid-oca-treatment-in-a-bleomycin-induced-pulmonary-fibrosis-rat-model
#18
P Comeglio, S Filippi, E Sarchielli, A Morelli, I Cellai, C Corno, A Pini, L Adorini, G B Vannelli, M Maggi, L Vignozzi
PURPOSE: We recently demonstrated a protective effect of the farnesoid X receptor agonist obeticholic acid (OCA) in rat models of bleomycin-induced pulmonary fibrosis (PF). Aim of the present study was to investigate whether the positive effects of OCA treatment are apparent also on ongoing bleomycin-induced PF, i.e., after 2 weeks of bleomycin administration. METHODS: Bleomycin-induced PF rats were treated 2 weeks after bleomycin administration with OCA or pirfenidone for two additional weeks...
June 19, 2018: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/29920471/microdomain-elements-of-airway-smooth-muscle-in-calcium-regulation-and-cell-proliferation
#19
C Zhao, A Y-H Wu, X Yu, Y Gu, Y Lu, X Song, N An, Y Zhang
Airway remodeling manifested by hyperplasia of airway smooth muscle cells (ASMCs) and other structural and functional changes is a pathological condition in asthma not addressed by current treatment. Ca2+ signaling is crucial for ASMC proliferation. Inositol-1,4,5-trisphosphate receptor (IP3R) and ryanodine receptor (RyR) mediate Ca2+ release from endoplasmic reticulum/sarcoplasmic reticulum (ER/SR). Upon sensing the depletion of Ca2+ in ER/SR, stromal interaction molecule 1 (STIM1) aggregates and redistributes at the microdomain of ER/SR-plasma membrane (PM) and activates Orai1, a component of the store-operated Ca2+ (SOC) channels, to initiate Ca2+ influx...
April 2018: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/29914989/ompr-regulator-of-burkholderia-multivorans-controls-mucoid-to-nonmucoid-transition-and-other-cell-envelope-properties-associated-with-persistence-in-the-cystic-fibrosis-lung
#20
Inês N Silva, Filipa D Pessoa, Marcelo J Ramires, Mário R Santos, Jörg D Becker, Vaughn S Cooper, Leonilde M Moreira
Bacteria from the Burkholderia cepacia complex grow in different natural and man-made environments and are feared opportunistic pathogens that cause chronic respiratory infections in cystic fibrosis patients. Previous studies showed that Burkholderia mucoid clinical isolates grown under stress conditions give rise to nonmucoid variants devoid of the exopolysaccharide cepacian. Here, we have determined that a major cause of the nonmucoid morphotype involves nonsynonymous mutations and small indels in the ompR gene encoding a response regulator of a two-component regulatory system...
June 18, 2018: Journal of Bacteriology
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