Pathophysiology of bronchial smooth muscle remodelling in asthma

Abstract

Whereas the role of bronchial smooth muscle remains controversial in healthy subjects its role is well established in asthmatics. Bronchial smooth muscle contraction induces airway narrowing. The smooth muscle also contributes to bronchial inflammation by secreting a range of inflammatory mediators, recruiting and activating inflammatory cells, such as mast cells or T-lymphocytes. In addition, bronchial smooth muscle mass is significantly increased in asthma. Such an increase has been related to a deposition of extracellular matrix proteins, and an increase in both cell size and number. However, the mechanisms of this smooth muscle remodelling are complex and not completely understood. The article will review recent data regarding the pathophysiology of bronchial smooth muscle remodelling in asthma.

Remodelage bronchique dans l’asthme

“…Cette observation met en exergue l'importance des relations entre épithélium et muscle lisse bronchique dans le contexte de l'unité épithélio-mésenchymateuse. Le remodelage des cellules musculaires lisses est caractérisé par une augmentation du dépôt des protéines de la matrice extracellulaire dans et autour du muscle et par une hypertrophie (augmentation de la taille) et une hyperplasie de ce muscle lisse bronchique (augmentation du nombre des cellules musculaires) [21]. D'autre part, les cellules épithéliales peuvent perdre leurs caractéristiques et acquérir des propriétés migratoires.…”

Connexins as therapeutic targets in lung disease

“…Lastly, mast cell infiltration into airway smooth muscle and the consequent muscle hypertrophy and hyperplasia represent an important feature of severe asthma [66]. Interestingly, Cx43 was also found to be expressed at the plasma membrane of murine mast cells [67].…”

Airway Smooth Muscle: Is There a Phenotype Associated with Asthma?

“…Importantly, sustained activation of PI3K and S6K1 at 12h discriminated ASM mitogens from non-mitogenic agonists that otherwise equally potentiate ERK1/2 at 1h (Krymskaya et al, 2000). Similar upstream pathways also induce ASM hypertrophy via mammalian target of rapamycin (mTOR), 4E-binding protein (4E-BP), the transcription factor eIF4E and S6 kinase or the inhibition of glycogen synthase kinase (GSK)-3 (Bara et al, 2010;Berger et al, 2005) Myofibroblasts are -smooth actin-positive mesenchymal precursors that transiently undergo reversible phenotypic differentiation to/from a variety of resident structural populations including ASM cells Brewster et al, 1990;Gizycki et al, 1997). These cells may migrate and differentiate into resident populations within ASM bundles, thus mediating hyperplasia.…”

“…Similarly, cADPR could stimulate CaM-mediated mechanisms leading to Ca 2+ -induced Ca 2+ release, enhancing the overall propagation of Ca 2+ oscillations throughout the cytosol. Several extracellular stimuli enhance CD38 expression and cADPR generation in human ASM; however, the precise mechanism by which extracellular cADPR is shunted to Ca 2+ intracellular stores remains unknown (Bara et al, 2010).…”