Glucocorticoid-induced Changes in Gene Expression of Airway Smooth Muscle in Patients with Asthma

Yick, Ching Yong; Zwinderman, Aeilko H.; Kunst, Peter W.A.; Grünberg, Katrien; Mauad, Thaís; Fluiter, Kees; Bel, Elisabeth H.; Lutter, René; Baas, Frank; Sterk, Peter J.

doi:10.1164/rccm.201210-1886oc

Cited by 58 publications

(54 citation statements)

References 39 publications

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“…Four of the genes (RPTOR, VANGL1, FAM129A, and LEPREL1) were associated with AHR. In a second study by this group, they were able to show that asthmatic ASM from patients treated with glucocorticoids had changes in the expression of genes related to cellular growth, proliferation, and development (Yick et al 2013). Interestingly, prednisone treatment was able to reverse the down-regulation of FAM129A, which was associated with AHR in the first study.…”

Section: Proteins Unrelated To Contractile Functionmentioning

confidence: 91%

“…Two recent studies using RNA-seq have identified changes in the expression of genes not directly related to ASM contractile function in asthmatic versus non-asthmatic tissue (Yick et al 2013(Yick et al , 2014. In their first paper, they micro-dissected ASM from asthmatics and found 174 genes differentially expressed when compared with the controls.…”

Section: Proteins Unrelated To Contractile Functionmentioning

confidence: 99%

See 1 more Smart Citation

Gene expression in asthmatic airway smooth muscle: a mixed bag

Pascoe

Swyngedouw

Seow

et al. 2015

Can. J. Physiol. Pharmacol.

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It has long been known that airway smooth muscle (ASM) contraction contributes significantly to the reversible airflow obstruction that defines asthma. It has also been postulated that phenotypic changes in ASM contribute to the airway hyperresponsiveness (AHR) that is a characteristic feature of asthma. Although there is agreement that the mass of ASM surrounding the airways is significantly increased in asthmatic compared with non-asthmatic airways, it is still uncertain whether there are quantitative or qualitative changes in the level of expression of the genes and proteins involved in the canonical contractile pathway in ASM that could account for AHR. This review will summarize past attempts at quantifying gene expression changes in the ASM of asthmatic lungs as well as non-asthmatic ASM cells stimulated with various inflammatory cytokines. The lack of consistent findings in asthmatic samples coupled with the relative concordance of results from stimulated ASM cells suggests that changes to the contractility of ASM tissues in asthma may be dependent on the presence of an inflammatory environment surrounding the ASM layer. Removal of the ASM from this environment could explain why hypercontractility is rarely seen ex vivo.Key words: asthma, airway smooth muscle, gene expression, protein expression, cytokines. Résumé :On sait depuis longtemps que la contraction du muscle lisse respiratoire (MLR) contribue de manière significative à l'obstruction réversible du débit d'air qui définit l'asthme. Il a aussi été postulé que des changements phénotypiques dans le MLR contribue à l'hyperréactivité bronchique (HRB) qui caractérise l'asthme. Même si l'on s'accorde sur le fait que la masse de MLR qui entoure les voies respiratoires est significativement plus importante en situation d'asthme comparativement à l'absence d'asthme, on ne sait pas encore avec certitude si des changements quantitatifs ou qualitatifs du niveau d'expression de gènes et de protéines impliqués dans les voies standards de régulation de la contraction chez le MLR pourraient expliquer l'HRB. Cet article de revue résumera les tentatives passées de quantification de changements d'expression génique dans des cellules de MLR de poumons asthmatiques et non asthmatiques, stimulées à l'aide de différentes cytokines inflammatoires. L'absence de données cohérentes issues d'échantillons asthmatiques, couplée à la concordance relative des résultats obtenus à partir de cellules de MLR stimulées suggère que les changements de contractilité du MLR dans l'asthme peuvent être dépendants de la présence d'un environnement inflammatoire autour de la couche de MLR. Le fait de retirer le MLR de son environnement pourrait expliquer pourquoi l'hyper-contractilité est rarement observée ex vivo. [Traduit par la Rédaction] Mots-clés : asthme, muscle lisse respiratoire, expression génique, expression protéique, cytokines.

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Section: Proteins Unrelated To Contractile Functionmentioning

confidence: 91%

Section: Proteins Unrelated To Contractile Functionmentioning

confidence: 99%

Gene expression in asthmatic airway smooth muscle: a mixed bag

Pascoe

Swyngedouw

Seow

et al. 2015

Can. J. Physiol. Pharmacol.

View full text Add to dashboard Cite

show abstract

“…Part of it is mediated by direct and indirect genomic (i.e. transcriptional) effects (Yick et al 2013), and part of it is exerted by a rapid non-genomic effect (Sun et al 2006). Indeed, acute or prolonged exposure to glucocorticoids reduces the contraction elicited by spasmogens and potentiates the relaxing response to b 2 -adrenergic receptor activation.…”

Section: Adrenalsmentioning

confidence: 99%

Endocrine regulation of airway contractility is overlooked

Bossé

2014

Journal of Endocrinology

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Asthma is a prevalent respiratory disorder triggered by a variety of inhaled environmental factors, such as allergens, viruses, and pollutants. Asthma is characterized by an elevated activation of the smooth muscle surrounding the airways, as well as a propensity of the airways to narrow excessively in response to a spasmogen (i.e. contractile agonist), a feature called airway hyperresponsiveness. The level of airway smooth muscle (ASM) activation is putatively controlled by mediators released in its vicinity. In asthma, many mediators that affect ASM contractility originate from inflammatory cells that are mobilized into the airways, such as eosinophils. However, mounting evidence indicates that mediators released by remote organs can also influence the level of activation of ASM, as well as its level of responsiveness to spasmogens and relaxant agonists. These remote mediators are transported through circulating blood to act either directly on ASM or indirectly via the nervous system by tuning the level of cholinergic activation of ASM. Indeed, mediators generated from diverse organs, including the adrenals, pancreas, adipose tissue, gonads, heart, intestines, and stomach, affect the contractility of ASM. Together, these results suggest that, apart from a paracrine mode of regulation, ASM is subjected to an endocrine mode of regulation. The results also imply that defects in organs other than the lungs can contribute to asthma symptoms and severity. In this review, I suggest that the endocrine mode of regulation of ASM contractility is overlooked.

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“…Three studies were published in the Journal in 2013 that identified new factors that may affect airway smooth muscle contraction and relaxation (55)(56)(57). Two of the studies applied multiple modalities to mouse, guinea pig, and human tissues and identified transmembrane protein 16A, a calcium-activated chloride channel, and Toll-like receptor 7, respectively, as factors that modify the response of airway smooth muscle to contractile agents (56,57).…”

Section: Pathways That Affect Smooth Musclementioning

confidence: 99%

“…Two of the studies applied multiple modalities to mouse, guinea pig, and human tissues and identified transmembrane protein 16A, a calcium-activated chloride channel, and Toll-like receptor 7, respectively, as factors that modify the response of airway smooth muscle to contractile agents (56,57). The third study combined laser capture microdissection of human airway biopsies and RNA sequencing to identify two genes (FAM129A and SYNPO2) that were significantly changed in expression with corticosteroids in asthma and which correlated with degree of airway hyper-responsiveness (55). Although technologically ambitious, that study was relatively small and did not pursue complementary modalities to assess the potential role of these genes.…”

Section: Pathways That Affect Smooth Musclementioning

confidence: 99%