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https://www.readbyqxmd.com/read/29018800/asthma-endotypes-and-an-overview-of-targeted-therapy-for-asthma
#1
REVIEW
Sarah Svenningsen, Parameswaran Nair
Guidelines for the management of severe asthma do not emphasize the measurement of the inflammatory component of airway disease to indicate appropriate treatments or to monitor response to treatment. Inflammation is a central component of asthma and contributes to symptoms, physiological, and structural abnormalities. It can be assessed by a number of endotyping strategies based on "omics" technology such as proteomics, transcriptomics, and metabolomics. It can also be assessed using simple cellular responses by quantitative cytometry in sputum...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/29017029/fgf10-hippo-epithelial-mesenchymal-crosstalk-maintains-and-recruits-lung-basal-stem-cells
#2
Thomas Volckaert, Tingting Yuan, Cho-Ming Chao, Harold Bell, Alina Sitaula, Luisa Szimmtenings, Elie El Agha, Diptiman Chanda, Susan Majka, Saverio Bellusci, Victor J Thannickal, Reinhard Fässler, Stijn P De Langhe
The lung harbors its basal stem/progenitor cells (BSCs) in the protected environment of the cartilaginous airways. After major lung injuries, BSCs are activated and recruited to sites of injury. Here, we show that during homeostasis, BSCs in cartilaginous airways maintain their stem cell state by downregulating the Hippo pathway (resulting in increased nuclear Yap), which generates a localized Fgf10-expressing stromal niche; in contrast, differentiated epithelial cells in non-cartilaginous airways maintain quiescence by activating the Hippo pathway and inhibiting Fgf10 expression in airway smooth muscle cells (ASMCs)...
October 9, 2017: Developmental Cell
https://www.readbyqxmd.com/read/28984468/tgf-%C3%AE-1-evokes-human-airway-smooth-muscle-cell-shortening-and-hyperresponsiveness-via-smad3
#3
Christie A Ojiaku, Gaoyuan Cao, Wanqu Zhu, Edwin J Yoo, Maya Shumyatcher, Blanca E Himes, Steven S An, Reynold A Panettieri
Transforming growth factor beta 1 (TGF-β1), a cytokine whose levels are elevated in the airways of patients with asthma, perpetuates airway inflammation and modulates airway structural cell remodeling. However, the role of TGF-β1 in excessive airway narrowing in asthma, or airway hyperresponsiveness (AHR), remains unclear. In this study, we set out to investigate the direct effects of TGF-β1 on human airway smooth muscle (HASM) cell shortening and hyperresponsiveness. The dynamics of AHR and single-cell excitation-contraction (E-C) coupling were measured in human precision-cut lung slices (hPCLS) and in isolated HASM cells using supravital microscopy and magnetic twisting cytometry (MTC), respectively...
October 6, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28982946/role-of-bronchodilation-and-pattern-of-breathing-in-increasing-expiratory-flow-during-progressive-hypercapnia-in-chronic-obstructive-pulmonary-disease
#4
Kevin E Finucane, Bhajan Singh
Hypercapnia (HC) in-vitro relaxes airway smooth muscle; in-vivo it increases respiratory effort, tidal expiratory flows (V'exp), and, by decreasing inspiratory duration (Ti), increases elastic recoil pressure (Pel) via lung visco-elasticity; however, its effect on airway resistance is uncertain. We examined the contributions of bronchodilation, Ti and expiratory effort to increasing V'exp ̇with progressive HC in 10 COPD subjects, mean FEV1 53% predicted. Lung volumes (Vl), V'exp, esophageal pressure (Pes), Ti and end tidal PCO2 (PetCO2) were measured during 6 tidal breaths followed by an inspiratory capacity (IC), breathing air and at 3 levels of HC...
October 5, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28982738/intranasal-administration-of-recombinant-progranulin-inhibits-bronchial-smooth-muscle-hyperresponsiveness-in-mouse-allergic-asthma
#5
Yoshihiko Chiba, Shunta Danno, Rena Suto, Wataru Suto, Yamato Yamane, Motohiko Hanazaki, Hiroshi Katayama, Hiroyasu Sakai
Progranulin (PGRN) is a growth factor with multiple biological functions, and has been suggested as an endogenous inhibitor of TNFα-mediated signaling. TNFα is believed as one of the important mediators of the pathogenesis of asthma, including airway hyperresponsiveness (AHR). In the present study, effects of recombinant PGRN on the TNFα-mediated signaling and the antigen-induced hyper-contractility were examined in bronchial smooth muscles (BSMs) both in vitro and in vivo. Cultured human BSM cells (hBSMCs) and male BALB/c mice were used...
October 5, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28978085/suppression-of-microrna-384-enhances-autophagy-of-airway-smooth-muscle-cells-in-asthmatic-mouse
#6
Zhe Cheng, Xi Wang, Lingling Dai, Liuqun Jia, Xiaogang Jing, Ying Liu, Huan Wang, Pengfei Li, Lin An, Meng Liu
Injury to airway smooth muscle (ASM) cells hallmarks the pathological progression of asthma, a chronic inflammatory airway disease. MicroRNAs (miRNAs) play essential roles in the development of asthma as well as airway remodeling. Here we studied the involvement of miRNAs in the regulation of autophagic survival of ASM cells and airway disorder. We analyzed autophagy-associated factors LC3 and Beclin-1 by RT-qPCR and protein blotting in purified airway smooth muscle cells from ovalbumin (OVA)-induced asthmatic mice...
September 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28971977/human-lung-branching-morphogenesis-is-orchestrated-by-the-spatio-temporal-distribution-of-acta2-sox2-and-sox9
#7
Soula Danopoulos, Irving Alonso, Matthew Thornton, Brendan Grubbs, Saverio Bellusci, David Warburton, Denise Al Alam
Lung morphogenesis relies on a number of important processes including proximal-distal patterning, cell proliferation, migration and differentiation, as well as epithelial-mesenchymal interactions. In mouse lung development, SOX2+ cells are localized in the proximal epithelium whereas SOX9+ cells are present in the distal epithelium. We show that in human lung, expression of these transcription factors differs, in that during the pseudoglandular stage distal epithelial progenitors at the tips co-express SOX2 and SOX9...
September 28, 2017: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/28970794/functional-cooperation-between-kca3-1-and-trpv4-channels-in-bronchial-smooth-muscle-cell-proliferation-associated-with-chronic-asthma
#8
Zhihua Yu, Yanxia Wang, Lu Qin, Hongzhuan Chen
Airway smooth muscle cells (SMC) proliferation contributes to the airways remodeling and irreversible airway obstruction during severe asthma, but the mechanisms of airway SMC proliferation are poorly understood. Intracellular Ca(2)(+) levels play an important role in regulating cell proliferation. We have previously reported KCa3.1 channels regulated human bronchial smooth muscle (HBSM) cells proliferation via the Ca(2+) influx as a consequence of membrane hyperpolarization. However, the role of potassium channels KCa3...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28960519/schisandrin-b-down-regulated-lncrna-bcyrn1-expression-of-airway-smooth-muscle-cells-by-improving-mir-150-expression-to-inhibit-the-proliferation-and-migration-of-asmc-in-asthmatic-rats
#9
Xiao-Yu Zhang, Xue-Yi Tang, Li-Jun Ma, Ya-Li Guo, Xiao-Su Li, Li-Min Zhao, Cui-Jie Tian, Dong-Jun Cheng, Zhuo-Chang Chen, Luo-Xian Zhang
OBJECTIVE: The mechanism of Schisandrin B on the proliferation and migration of airway smooth muscle cells (ASMCs) in asthmatic rats was explored. METHODS: SD rats were divided into three groups: control (group 1), model (group 2) and model + Schisandrin B (group 3). miR-150 and lncRNA BCYRN1 levels were measured by qRT-PCR. The combination of BCYRN1 and miR-150 was detected by RNA pull down. ASMCs' viability/proliferation/migration were examined by WST-1 assay and 24-well Transwell system...
September 27, 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28960335/airway-pathology-in-severe-asthma-is-related-to-airflow-obstruction-but-not-symptom-control
#10
Diogenes S Ferreira, Regina M Carvalho-Pinto, Marcelo G Gregório, Raquel Annoni, Aila M Teles, Monique Buttignol, Bianca B Araújo-Paulino, Edgard H Katayama, Bianca L Oliveira, Heloisa S Del Frari, Alberto Cukier, Marisa Dolhnikoff, Rafael Stelmach, Klaus F Rabe, Thais Mauad
BACKGROUND: Patients with asthma present structural and inflammatory alterations that are believed to play a role in disease severity. However, airway remodeling and inflammation have not been extensively investigated in relation to both symptom control and airflow obstruction in severe asthmatics. We aimed to investigate several inflammatory and structural pathological features in bronchial biopsies of severe asthmatics that could be related to symptom control and airflow obstruction after standardized treatment...
September 27, 2017: Allergy
https://www.readbyqxmd.com/read/28958904/atf6%C3%AE-regulates-airway-hyperreactivity-smooth-muscle-proliferation-and-contractility
#11
Hirotoshi Unno, Marina Miller, Peter Rosenthal, Andrew Beppu, Sudipta Das, David H Broide
ORMDL3 on chromosome 17q21 is highly linked to asthma and regulates several downstream pathways including ATF6α. We demonstrated that ATF6α in airway smooth muscle (ASM) plays an important role in ASM contractility, proliferation, and AHR.
September 26, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28957813/nicotine-induced-airway-smooth-muscle-cell-proliferation-involves-trpc6-dependent-calcium-influx-via-%C3%AE-7-nachr
#12
Wei Hong, Gongyong Peng, Binwei Hao, Baoling Liao, Zhuxiang Zhao, Yumin Zhou, Fang Peng, Xiuqin Ye, Lingmei Huang, Mengning Zheng, Jinding Pu, Chunxiao Liang, Erkang Yi, Huanhuan Peng, Bing Li, Pixin Ran
BACKGROUND/AIMS: The proliferation of human bronchial smooth muscle cells (HBSMCs) is a key pathophysiological component of airway remodeling in chronic obstructive pulmonary disease (COPD) for which pharmacotherapy is limited, and only slight improvements in survival have been achieved in recent decades. Cigarette smoke is a well-recognized risk factor for COPD; however, the pathogenesis of cigarette smoke-induced COPD remains incompletely understood. This study aimed to investigate the mechanisms by which nicotine affects HBSMC proliferation...
September 29, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28950943/%C3%AE-2-adrenoceptor-function-in-asthma
#13
Yassine Amrani, Peter Bradding
β2-adrenoceptor agonists, often used in combination with corticosteroids, have been extensively used for the treatment of asthma. However, concerns have been raised regarding their adverse effects and safety including poor asthma control, life-threatening exacerbations, exacerbations that often require hospitalization, and asthma-related deaths. The question as to whether these adverse effects relate to the loss of their bronchoprotective action remains an interesting possibility. In the chapter, we will review the experimental evidence that describes the different potential factors and associated mechanisms that can blunt the therapeutic action of β2-adrenoceptor agonists in asthma...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28947081/chronic-il-33-expression-predisposes-to-viral-induced-exacerbations-of-asthma-by-increasing-type-2-inflammation-and-dampening-antiviral-immunity
#14
Rhiannon B Werder, B Biomed Sci, Vivian Zhang, Jason P Lynch, Natale Snape, John W Upham, Kirsten Spann, Simon Phipps
BACKGROUND: Rhinovirus infection triggers acute exacerbations of asthma. IL-33 is an instructive cytokine of type-2 inflammation whose expression is associated with viral load during experimental rhinovirus infection of asthmatic subjects. OBJECTIVE: To determine whether anti-IL-33 therapy is effective during disease progression, established disease, or viral exacerbation using a preclinical model of chronic asthma and in vivo human primary airway epithelial cells (AECs)...
September 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28943877/%C3%AE-catenin-directs-nuclear-factor-%C3%AE%C2%BAb-p65-output-via-creb-binding-protein-p300-in-human-airway-smooth-muscle
#15
Tim Koopmans, Roos Eilers, Mark Menzen, Andrew Halayko, Reinoud Gosens
β-Catenin is a multifunctional protein that apart from its role in proliferative and differentiation events, also acts upon inflammatory processes, mainly via interaction with nuclear factor-κB (NF-κB). However, there is still controversy as to whether β-catenin facilitates or represses NF-κB output. Insights into the molecular mechanisms underlying the interaction between β-catenin and NF-κB have highlighted the cofactors CREB-binding protein (CBP) and p300 as important candidates. Here, we hypothesized that the interaction of β-catenin with CBP/p300 directs NF-κB output...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28942149/fibulin-5-promotes-airway-smooth-muscle-cell-proliferation-and-migration-via-modulating-hippo-yap-taz-pathway
#16
Jia Fu, Mao Zheng, Xiaofang Zhang, Yufeng Zhang, Yao Chen, Hua Li, Xiaowei Wang, Jinjun Zhang
Asthma is a common chronic disease mainly occurs from childhood. Increased airway smooth muscle mass is involved in the pathogenesis of asthma. Fibulin-5 was upregulated in the lung tissues of patients with COPD and idiopathic pulmonary fibrosis. This study aimed to investigate Fibulin-5 expression in asthmatic patients and the effect and mechanism of Fibulin-5 on the proliferation and migration of airway smooth muscle cells (ASMCs). The expression of Fibulin-5, YAP, and TAZ in the induced sputum of 38 asthmatic children (19 mild and 19 moderate asthmatics) and 19 healthy controls was determined...
November 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28937232/physiology-of-nitric-oxide-in-the-respiratory-system
#17
M Antosova, D Mokra, L Pepucha, J Plevkova, T Buday, M Sterusky, A Bencova
Nitric oxide (NO) is an important endogenous neurotransmitter and mediator. It participates in regulation of physiological processes in different organ systems including airways. Therefore, it is important to clarify its role in the regulation of both airway and vascular smooth muscle, neurotransmission and neurotoxicity, mucus transport, lung development and in the. surfactant production. The bioactivity of NO is highly variable and depends on many factors: the presence and activity of NO-producing enzymes, activity of competitive enzymes (e...
September 22, 2017: Physiological Research
https://www.readbyqxmd.com/read/28924004/basic-fibroblast-growth-factor-2-is-a-determinant-of-cd4-t-cell-airway-smooth-muscle-cell-communication-through-membrane-conduits
#18
Soroor Farahnak, Toby K McGovern, Rachael Kim, Michael O'Sullivan, Brian Chen, Minhyoung Lee, Haruka Yoshie, Anna Wang, Joyce Jang, Saba Al Heialy, Anne-Marie Lauzon, James G Martin
Activated CD4 T cells connect to airway smooth muscle cells (ASMCs) in vitro via lymphocyte-derived membrane conduits (LMCs) structurally similar to membrane nanotubes with unknown intercellular signals triggering their formation. We examined the structure and function of CD4 T cell-derived LMCs, and we established a role for ASMC-derived basic fibroblast growth factor 2 (FGF2b) and FGF receptor (FGFR)1 in LMC formation. Blocking FGF2b's synthesis and FGFR1 function reduced LMC formation. Mitochondrial flux from ASMCs to T cells was partially FGF2b and FGFR1 dependent...
September 18, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28921504/g%C3%AE-12-facilitates-carbachol-induced-shortening-in-human-airway-smooth-muscle-by-modulating-phosphoinositide-3-kinase-mediated-activation-in-a-rhoa-dependent-manner
#19
Edwin J Yoo, Gaoyuan Cao, Cynthia J Koziol-White, Christie A Ojiaku, Krishna Sunder, Joseph A Jude, James V Michael, Hong Lam, Ivan Pushkarsky, Robert Damoiseaux, Dino Di Carlo, Kwangmi Ahn, Steven S An, Raymond B Penn, Reynold A Panettieri
BACKGROUND AND PURPOSE: Phosphoinositide 3-kinase (PI3K)-dependent activation of Rho kinase (ROCK) is necessary for agonist-induced human airway smooth muscle cell (HASMC) contraction, and inhibition of PI3K promotes bronchodilation of human small airways. The upstream mechanisms driving agonist-mediated PI3K/ROCK axis activation, however, remain unclear. Given the capacity of G12 family proteins to activate ROCK pathways in other cell types (Riobo and Manning, 2005), the role of G12 proteins in modulating M3 muscarinic acetylcholine receptor (M3R)-stimulated PI3K/ROCK activation and HASMC contraction was examined...
September 17, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28911970/mesenchymal-stem-cells-alleviate-oxidative-stress-induced-mitochondrial-dysfunction-in-the-airways
#20
Xiang Li, Charalambos Michaeloudes, Yuelin Zhang, Coen H Wiegman, Ian M Adcock, Qizhou Lian, Judith C W Mak, Pankaj K Bhavsar, Kian Fan Chung
BACKGROUND: Oxidative stress-induced mitochondrial dysfunction can contribute to inflammation and remodeling in patients with chronic obstructive pulmonary disease (COPD). Mesenchymal stem cells protect against lung damage in animal models of COPD. It is unknown whether these effects occur through attenuating mitochondrial dysfunction in airway cells. OBJECTIVE: We sought to examine the effect of induced pluripotent stem cell-derived mesenchymal stem cells (iPSC-MSCs) on oxidative stress-induce mitochondrial dysfunction in human airway smooth muscle cells (ASMCs) in vitro and in mouse lungs in vivo...
September 11, 2017: Journal of Allergy and Clinical Immunology
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