Airway structural components drive airway smooth muscle remodeling in asthma.
Chronic asthma is an inflammatory airways disease characterized by pathological changes in the airway smooth muscle (ASM) bundle that contribute to airway obstruction and hyperresponsiveness. Remodeling of the ASM is associated with an increased smooth muscle mass, involving components of cellular hypertrophy and hyperplasia, and changes in the phenotype of the muscle that facilitate proliferative, synthetic and contractile functions. These changes are considered major contributing factors to the pathophysiology of asthma, because of their role in exaggerated airway narrowing. The mechanisms that regulate changes in ASM mass and phenotype are incompletely understood, but likely involve the regulatory role of mediators and growth factors secreted from inflammatory cells on ASM cell proliferation and phenotype. An alternative hypothesis is that cellular and structural components that together constitute the airway wall, such as the airway epithelium, airway nerves, and the extracellular matrix, interact with the ASM bundle to facilitate changes in smooth muscle phenotype and function that drive remodeling under inflammatory conditions. This review discusses the mechanisms by which structural components of the airway wall communicate with the ASM bundle to regulate remodeling and discusses these mechanisms in the context of the pathophysiology of asthma.
Dekkers
Bart G J
BG
Department of Molecular Pharmacology, University of Groningen, Groningen, The Netherlands.
Maarsingh
Harm
H
Meurs
Herman
H
Gosens
Reinoud
R
D056151:Airway Remodeling / Q000502:physiology*; D001249:Asthma / Q000503:physiopathology*; D002908:Chronic Disease; D005109:Extracellular Matrix / Q000502:physiology; D006801:Humans; D009130:Muscle, Smooth / Q000503:physiopathology; D010275:Parasympathetic Nervous System / Q000503:physiopathology; D020545:Respiratory Mucosa / Q000503:physiopathology; D012137:Respiratory System / Q000294:innervation / Q000503:physiopathology*