Inhaled corticosteroid prevents the thickening of airway smooth muscle in murine model of chronic asthma

2008 ◽  
Vol 21 (1) ◽  
pp. 14-19 ◽  
Author(s):  
Sook Young Lee ◽  
Jin Sook Kim ◽  
Jung Mi Lee ◽  
Soon Seok Kwon ◽  
Kwan Hyung Kim ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Murine Model ◽  
Chronic Asthma ◽  
Inhaled Corticosteroid

Effect of Imatinib on Airway Smooth Muscle Thickening in a Murine Model of Chronic Asthma

2011 ◽  
Vol 155 (3) ◽  
pp. 243-251 ◽  
Author(s):  
Chin Kook Rhee ◽  
Jin Woo Kim ◽  
Chan Kwon Park ◽  
Joo Sang Kim ◽  
Ji Young Kang ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Smooth Muscle ◽  
Murine Model ◽  
Chronic Asthma

Hypertrophic Airway Smooth Muscle Mass Correlates with Increased Airway Responsiveness in a Murine Model of Asthma

2012 ◽  
Vol 46 (4) ◽  
pp. 532-540 ◽  
Author(s):  
Pamela J. Plant ◽  
Michelle L. North ◽  
Andrew Ward ◽  
Michael Ward ◽  
Nivedita Khanna ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Muscle Mass ◽  
Airway Smooth Muscle ◽  
Murine Model ◽  
Airway Responsiveness

Potential role for phenotypic modulation of bronchial smooth muscle ceils in chronic asthma

1994 ◽  
Vol 72 (11) ◽  
pp. 1448-1457 ◽  
Author(s):  
Andrew J. Halayko ◽  
Newman L. Stephens
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Airway Smooth Muscle ◽  
Muscle Cells ◽  
Airway Smooth Muscle Cells ◽  
Potential Contribution ◽  
Chronic Asthma ◽  
Phenotypic Modulation ◽  
Bronchial Smooth Muscle

Asthma is considered to be a chronic inflammatory disease of the airways and is highlighted by excessive airway narrowing in response to various stimuli. Subepithelial fibrosis and increased airway smooth muscle mass are characteristic pathological features of the disease. Airway remodelling in asthma involves cellular hyperplasia and hypertrophy of bronchial myocytes. Smooth muscle cells from a variety of tissues have been shown to be multifunctional mesenchymal cells capable of expressing considerable phenotypic plasticity in vivo in response to injury and pathological stimuli. The growth response of vascular smooth muscle cells following arterial injury has been fairly well characterized, and it appears many of the chemical mediators responsible are common to the inflamed bronchi seen in asthmatics. Specific studies regarding the effects of phenotypic modulation of airway smooth muscle and the potential contribution of this phenomenon to the pathogenesis of chronic asthma have not been carried out. Limited evidence, some indirect, suggests that contractile properties of smooth muscle from inflamed tissues are altered; if this is the case in asthma, then considerations of the effects of airway smooth muscle hypertrophy should be broadened beyond that of only contributing to bronchial hyperresponsiveness via an increase in bronchial wall thickness. Recruitment and modulation of smooth muscle cells to functionally different phenotypes, which contribute to fibrosis by secreting extracellular matrix materials and promote cellular hyperplasia by producing growth factors, are known to occur in atherogenic blood vessels; and evidence suggests that airway smooth muscle cells might play a similar role in asthma. We report the identification of markers of differentiation for airway smooth muscle cells. These markers should be useful tools in the elucidation of phenotypic heterogeneity of smooth muscle in asthmatic airways and, thereby, allow for the definition of a clearer role for bronchial smooth muscle cells in the pathogenesis of chronic asthma.Key words: airway smooth muscle cells, asthma, phenotype, pathogenesis, proliferation.

scholarly journals Exchange protein directly activated by cAMP (Epac) protects against airway inflammation and airway remodeling in asthmatic mice

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Yi-fei Chen ◽  
Ge Huang ◽  
Yi-min Wang ◽  
Ming Cheng ◽  
Fang-fang Zhu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Airway Inflammation ◽  
Airway Smooth Muscle ◽  
Airway Hyperresponsiveness ◽  
Inflammatory Cell ◽  
Acute Asthma ◽  
Airway Remodeling ◽  
Chronic Asthma ◽  
Mice Model

Abstract Background β2 receptor agonists induce airway smooth muscle relaxation by increasing intracellular cAMP production. PKA is the traditional downstream signaling pathway of cAMP. Exchange protein directly activated by cAMP (Epac) was identified as another important signaling molecule of cAMP recently. The role of Epac in asthmatic airway inflammation and airway remodeling is unclear. Methods We established OVA-sensitized and -challenged acute and chronic asthma mice models to explore the expression of Epac at first. Then, airway inflammation and airway hyperresponsiveness in acute asthma mice model and airway remodeling in chronic asthma mice model were observed respectively after treatment with Epac-selective cAMP analogue 8-pCPT-2′-O-Me-cAMP (8pCPT) and Epac inhibitor ESI-09. Next, the effects of 8pCPT and ESI-09 on the proliferation and apoptosis of in vitro cultured mouse airway smooth muscle cells (ASMCs) were detected with CCK-8 assays and Annexin-V staining. Lastly, the effects of 8pCPT and ESI-09 on store-operated Ca2+ entry (SOCE) of ASMCs were examined by confocal Ca2+ fluorescence measurement. Results We found that in lung tissues of acute and chronic asthma mice models, both mRNA and protein expression of Epac1 and Epac2, two isoforms of Epac, were lower than that of control mice. In acute asthma mice model, the airway inflammatory cell infiltration, Th2 cytokines secretion and airway hyperresponsiveness were significantly attenuated by 8pCPT and aggravated by ESI-09. In chronic asthma mice model, 8pCPT decreased airway inflammatory cell infiltration and airway remodeling indexes such as collagen deposition and airway smooth muscle cell proliferation, while ESI-09 increased airway inflammation and airway remodeling. In vitro cultured mice ASMCs, 8pCPT dose-dependently inhibited, whereas ESI-09 promoted ASMCs proliferation. Interestingly, 8pCPT promoted the apoptosis of ASMCs, whereas ESI-09 had no effect on ASMCs apoptosis. Lastly, confocal Ca2+ fluorescence examination found that 8pCPT could inhibit SOCE in ASMCs at 100 μM, and ESI-09 promoted SOCE of ASMCs at 10 μM and 100 μM. In addition, the promoting effect of ESI-09 on ASMCs proliferation was inhibited by store-operated Ca2+ channel blocker, SKF-96365. Conclusions Our results suggest that Epac has a protecting effect on asthmatic airway inflammation and airway remodeling, and Epac reduces ASMCs proliferation by inhibiting SOCE in part.

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