JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Clonally expanded human airway smooth muscle cells exhibit morphological and functional heterogeneity.
Respir. Res.
PUBLISHED: 01-30-2014
Show Abstract
Hide Abstract
Mesenchyme-derived airway cell populations including airway smooth muscle (ASM) cells, fibroblasts and myofibroblasts play key roles in the pathogenesis of airway inflammation and remodeling. Phenotypic and functional characterisation of these cell populations are confounded by their heterogeneity in vitro. It is unclear which mechanisms underlie the creation of these different sub-populations.The study objectives were to investigate whether ASM cells are capable of clonal expansion and if so (i) what proportion possess this capability and (ii) do clonal populations exhibit variation in terms of morphology, phenotype, proliferation rates and pro-relaxant or pro-contractile signaling pathways.
Related JoVE Video
The role of inflammation resolution speed in airway smooth muscle mass accumulation in asthma: insight from a theoretical model.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Despite a large amount of in vitro data, the dynamics of airway smooth muscle (ASM) mass increase in the airways of patients with asthma is not well understood. Here, we present a novel mathematical model that describes qualitatively the growth dynamics of ASM cells over short and long terms in the normal and inflammatory environments typically observed in asthma. The degree of ASM accumulation can be explained by an increase in the rate at which ASM cells switch between non-proliferative and proliferative states, driven by episodic inflammatory events. Our model explores the idea that remodelling due to ASM hyperplasia increases with the frequency and magnitude of these inflammatory events, relative to certain sensitivity thresholds. It highlights the importance of inflammation resolution speed by showing that when resolution is slow, even a series of small exacerbation events can result in significant remodelling, which persists after the inflammatory episodes. In addition, we demonstrate how the uncertainty in long-term outcome may be quantified and used to design an optimal low-risk individual anti-proliferative treatment strategy. The model shows that the rate of clearance of ASM proliferation and recruitment factors after an acute inflammatory event is a potentially important, and hitherto unrecognised, target for anti-remodelling therapy in asthma. It also suggests new ways of quantifying inflammation severity that could improve prediction of the extent of ASM accumulation. This ASM growth model should prove useful for designing new experiments or as a building block of more detailed multi-cellular tissue-level models.
Related JoVE Video
HTR4 gene structure and altered expression in the developing lung.
Respir. Res.
PUBLISHED: 06-13-2013
Show Abstract
Hide Abstract
Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT?R) gene (HTR4) associated with lung function. The aims of this study were to i) investigate the expression profile of HTR4 in adult and fetal lung tissue and cultured airway cells, ii) further define HTR4 gene structure and iii) explore the potential functional implications of key SNPs using a bioinformatic approach.
Related JoVE Video
GSTCD and INTS12 regulation and expression in the human lung.
PLoS ONE
PUBLISHED: 01-01-2013
Show Abstract
Hide Abstract
Genome-Wide Association Study (GWAS) meta-analyses have identified a strong association signal for lung function, which maps to a region on 4q24 containing two oppositely transcribed genes: glutathione S-transferase, C-terminal domain containing (GSTCD) and integrator complex subunit 12 (INTS12). Both genes were found to be expressed in a range of human airway cell types. The promoter regions and transcription start sites were determined in mRNA from human lung and a novel splice variant was identified for each gene. We obtained the following evidence for GSTCD and INTS12 co-regulation and expression: (i) correlated mRNA expression was observed both via Q-PCR and in a lung expression quantitative trait loci (eQTL) study, (ii) induction of both GSTCD and INTS12 mRNA expression in human airway smooth muscle cells was seen in response to TGF?1, (iii) a lung eQTL study revealed that both GSTCD and INTS12 mRNA levels positively correlate with percent predicted FEV1, and (iv) FEV1 GWAS associated SNPs in 4q24 were found to act as an eQTL for INTS12 in a number of tissues. In fixed sections of human lung tissue, GSTCD protein expression was ubiquitous, whereas INTS12 expression was predominantly in epithelial cells and pneumocytes. During human fetal lung development, GSTCD protein expression was observed to be highest at the earlier pseudoglandular stage (10-12 weeks) compared with the later canalicular stage (17-19 weeks), whereas INTS12 expression levels did not alter throughout these stages. Knowledge of the transcriptional and translational regulation and expression of GSTCD and INTS12 provides important insights into the potential role of these genes in determining lung function. Future work is warranted to fully define the functions of INTS12 and GSTCD.
Related JoVE Video
Real time analysis of ?(2)-adrenoceptor-mediated signaling kinetics in human primary airway smooth muscle cells reveals both ligand and dose dependent differences.
Respir. Res.
PUBLISHED: 03-22-2011
Show Abstract
Hide Abstract
?2-adrenoceptor agonists elicit bronchodilator responses by binding to ?2-adrenoceptors on airway smooth muscle (ASM). In vivo, the time between drug administration and clinically relevant bronchodilation varies significantly depending on the agonist used. Our aim was to utilise a fluorescent cyclic AMP reporter probe to study the temporal profile of ?2-adrenoceptor-mediated signaling induced by isoproterenol and a range of clinically relevant agonists in human primary ASM (hASM) cells by using a modified Epac protein fused to CFP and a variant of YFP.
Related JoVE Video
Can lineage-specific markers be identified to characterize mesenchyme-derived cell populations in the human airways?
Am. J. Physiol. Lung Cell Mol. Physiol.
PUBLISHED: 04-30-2010
Show Abstract
Hide Abstract
Mesenchyme-derived cells in the airway wall including airway smooth muscle cells, fibroblasts, and myofibroblasts are known to play important roles in airway remodeling. The lack of specific phenotypical markers makes it difficult to define these cell populations in primary cultures. Most relevant studies to date have used animal airway tissues, vascular tissues, or transformed cell lines with only limited studies attempting to phenotypically characterize human airway mesenchymal cells. The objectives of this study were to evaluate reported markers and identify novel markers to define these cell types. We could not identify any specific marker to define these cell populations in vitro that permitted unequivocal identification using immunocytochemistry. However, characteristic filamentous alpha-smooth muscle actin distribution was observed in a significant ( approximately 25%) proportion of human airway smooth muscle cells, whereas this was not observed in airway fibroblasts. A significantly higher proportion of airway fibroblasts expressed alpha(1)- and alpha(2)-integrin receptors compared with human airway smooth muscle cells as assessed by fluorescence activated cell sorting. Global gene expression profiling identified aldo-keto reductase 1C3 (AKR1C3) and cathepsin K as being novel markers to define airway smooth muscle cells, whereas integrin-alpha(8) (ITGA8) and thromboxane synthase 1 (TBXAS1) were identified as novel airway fibroblast-specific markers, and these findings were validated by RT-PCR. Ex vivo studies in human airway tissue sections identified high-molecular weight caldesmon and alpha-smooth muscle actin as being expressed in smooth muscle bundles, whereas ITGA8 and TBXAS1 were absent from these.
Related JoVE Video
Emerging airway smooth muscle targets to treat asthma.
Pulm Pharmacol Ther
Show Abstract
Hide Abstract
Asthma is characterized in part by variable airflow obstruction and non-specific hyperresponsiveness to a variety of bronchoconstrictors, both of which are mediated by the airway smooth muscle (ASM). The ASM is also involved in the airway inflammation and airway wall remodeling observed in asthma. For all these reasons, the ASM provides an important target for the treatment of asthma. Several classes of drugs were developed decades ago which targeted the ASM - including ?-agonists, anti-cholinergics, anti-histamines and anti-leukotrienes - but no substantially new class of drug has appeared recently. In this review, we summarize the on-going work of several laboratories aimed at producing novel targets and/or tools for the treatment of asthma. These range from receptors and ion channels on the ASM plasmalemma, to intracellular effectors (particularly those related to cyclic nucleotide signaling, calcium-homeostasis and phosphorylation cascades), to anti-IgE therapy and outright destruction of the ASM itself.
Related JoVE Video
cAMP regulation of airway smooth muscle function.
Pulm Pharmacol Ther
Show Abstract
Hide Abstract
Agonists activating ?(2)-adrenoceptors (?(2)ARs) on airway smooth muscle (ASM) are the drug of choice for rescue from acute bronchoconstriction in patients with both asthma and chronic obstructive pulmonary disease (COPD). Moreover, the use of long-acting ?-agonists combined with inhaled corticosteroids constitutes an important maintenance therapy for these diseases. ?-Agonists are effective bronchodilators due primarily to their ability to antagonize ASM contraction. The presumed cellular mechanism of action involves the generation of intracellular cAMP, which in turn can activate the effector molecules cAMP-dependent protein kinase (PKA) and Epac. Other agents such as prostaglandin E(2) and phosphodiesterase inhibitors that also increase intracellular cAMP levels in ASM, can also antagonize ASM contraction, and inhibit other ASM functions including proliferation and migration. Therefore, ?(2)ARs and cAMP are key players in combating the pathophysiology of airway narrowing and remodeling. However, limitations of ?-agonist therapy due to drug tachyphylaxis related to ?(2)AR desensitization, and recent findings regarding the manner in which ?(2)ARs and cAMP signal, have raised new and interesting questions about these well-studied molecules. In this review we discuss current concepts regarding ?(2)ARs and cAMP in the regulation of ASM cell functions and their therapeutic roles in asthma and COPD.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.