Airway Smooth Muscle Biology and Therapeutics in Respiratory Health

Airway smooth muscle (ASM) plays a central role in the control of airway calibre and the pathogenesis of obstructive lung diseases. ASM cells surround the bronchial tree and respond to neural, inflammatory and mechanical stimuli by contracting or relaxing, thereby modulating airway resistance. Beyond its contractile function, ASM exhibits phenotypic plasticity: under chronic inflammatory cues, cells adopt a synthetic profile characterised by enhanced proliferation, secretion of matrix proteins and pro-inflammatory mediators. This contributes to airway remodelling – thickening of the airway wall, increased muscle mass, mucus hyperproduction and extracellular matrix deposition – which underlies progressive airflow obstruction in asthma and chronic obstructive pulmonary disease (COPD). Key signalling pathways that regulate ASM function include G-protein-coupled receptor cascades, cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA), mitogen-activated protein kinases, phosphodiesterases (PDEs) and lipid kinases. Therapeutic approaches aim to relax ASM acutely through β2-adrenoceptor agonists or muscarinic antagonists, while emerging strategies target ASM proliferation and remodelling, including inhibitors of specific kinases, modulators of receptor signalling and agents that restore defective relaxant responses. Advances in understanding ASM biochemistry and mechanics have uncovered novel allosteric sites on the β2-adrenoceptor, lipid signalling enzymes that regulate proliferation, and dual-acting small molecules that attenuate inflammation whilst reversing remodelling. These developments promise more effective and durable interventions to preserve lung function and improve quality of life in patients with obstructive respiratory diseases.

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Airway Smooth Muscle Biology and Therapeutics in Respiratory Health publication trend

The graph below shows the total number of articles in airway smooth muscle biology and therapeutics in respiratory health across all publications each year (not limited to Nature Index journals).

Technical terms

Airway remodelling: Structural alterations in the bronchial wall including increased smooth muscle mass, subepithelial fibrosis and mucus gland enlargement.

Bronchoprotection: The prevention or reduction of bronchoconstriction in response to stimuli.

Allosteric modulator: A compound that binds to a receptor at a site distinct from the active (orthosteric) site, altering receptor responsiveness to endogenous ligands.

Diacylglycerol kinase (DGK): An enzyme converting diacylglycerol into phosphatidic acid, thereby regulating lipid-mediated signalling in cells.

Protein kinase A (PKA): A cAMP-dependent kinase that phosphorylates target proteins to modulate smooth muscle relaxation and gene expression.

Phosphodiesterase (PDE): Enzymes that degrade cyclic nucleotides (cAMP, cGMP), thus controlling intracellular signalling and smooth muscle tone.

Proliferation: Increase in cell number due to cell division, contributing to muscle mass expansion in chronic airway disease.

References

1. Allosteric modulator potentiates β2AR agonist-promoted bronchoprotection in asthma models. Journal of Clinical Investigation (2023).
2. Crosstalk between diacylglycerol kinase and protein kinase A in the regulation of airway smooth muscle cell proliferation. Respiratory Research (2023).
3. Inhaled pan-phosphodiesterase inhibitors ameliorate ovalbumin-induced airway inflammation and remodeling in murine model of allergic asthma. International Immunopharmacology (2023).