title: Airway smooth muscle in asthma: linking contraction and mechanotransduction to disease pathogenesis and remodelling.
abstract: Asthma is an obstructive airway disease, with a heterogeneous and multifactorial pathogenesis. Although generally considered to be a disease principally driven by chronic inflammation, it is becoming increasingly recognised that the immune component of the pathology poorly correlates with the clinical symptoms of asthma, thus highlighting a potentially central role for non-immune cells. In this context airway smooth muscle (ASM) may be a key player, as it comprises a significant proportion of the airway wall and is the ultimate effector of acute airway narrowing. Historically, the contribution of ASM to asthma pathogenesis has been contentious, yet emerging evidence suggests that ASM contractile activation imparts chronic effects that extend well beyond the temporary effects of bronchoconstriction. In this review article we describe the effects that ASM contraction, in combination with cellular mechanotransduction and novel contraction-inflammation synergies, contribute to asthma pathogenesis. Specific emphasis will be placed on the effects that ASM contraction exerts on the mechanical properties of the airway wall, as well as novel mechanisms by which ASM contraction may contribute to more established features of asthma such as airway wall remodelling.
authors: School of Anatomy, Physiology and Human Biology, University of Western Australia, WA, Australia.
authors: Peter B
authors: PB
authors: Noble
authors: Center for Heart Lung Innovation, University of British Columbia, BC, Canada.
authors: Chris D
authors: CD
authors: Pascoe
authors: Center for Heart Lung Innovation, University of British Columbia, BC, Canada; Bioengineering College, Chongqing University, Chongqing, China.
authors: Bo
authors: B
authors: Lan
authors: Department of Respiratory Medicine, Nagoya University, Aichi, Japan.
authors: Satoru
authors: S
authors: Ito
authors: Department of Molecular Pharmacology, University of Groningen, The Netherlands.
authors: Loes E M
authors: LE
authors: Kistemaker
authors: Division of Respiratory Medicine, University of Nottingham, United Kingdom.
authors: Amanda L
authors: AL
authors: Tatler
authors: Center for Translational Medicine, Thomas Jefferson University, Philadelphia, PA, USA.
authors: Tonio
authors: T
authors: Pera
authors: School of Mathematical Sciences, University of Nottingham, United Kingdom.
authors: Bindi S
authors: BS
authors: Brook
authors: Department of Molecular Pharmacology, University of Groningen, The Netherlands.
authors: Reinoud
authors: R
authors: Gosens
authors: Department of Physiology, University of Manitoba, MB, Canada; Biology of Breathing, Manitoba Institute of Child Health, MB, Canada. Electronic address: Adrian.West@umanitoba.ca.
authors: Adrian R
authors: AR
authors: West
mesh_terms: D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D001249:Asthma / Q000209:etiology / Q000503:physiopathology*; D016084:Bronchoconstriction / Q000502:physiology; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology*; D012143:Respiratory Physiological Phenomena
keywords: Airway mechanics; Airway smooth muscle; Asthma; Contraction; Mechanotransduction