Airway Smooth Muscle Dynamics in Asthma and COPD Pathophysiology

Airway smooth muscle (ASM) lies at the core of bronchomotor tone and undergoes profound alterations in chronic airway diseases. In asthma and chronic obstructive pulmonary disease (COPD), ASM exhibits exaggerated contractility, enhanced proliferative capacity and increased migration, contributing to airway hyperresponsiveness and fixed airflow limitation. Key signalling cascades—among them calcium handling, Rho/ROCK activation and p38 MAPK pathways—drive cytoskeletal reorganisation, secretion of pro-inflammatory mediators and extracellular matrix deposition. Concomitantly, emerging regulatory networks involving microRNAs and long noncoding RNAs fine-tune gene expression underlying remodelling. The interplay between epithelial injury, immune cell infiltration and ASM plasticity establishes a self-perpetuating cycle of inflammation and structural change. Therapeutic approaches now extend beyond bronchodilation towards anti-remodelling strategies—targeting growth factors, epigenetic modifiers and post-translational processes—to restore airway calibre and improve long-term outcomes. Understanding ASM dynamics is therefore essential for the development of precision interventions in globally prevalent airway disorders.

Research from Nature Portfolio

Recent studies have shown that SUMOylation of ROCK2 at a specific lysine residue potentiates RhoA–ROCK signalling, driving goblet cell metaplasia, mucus hypersecretion and airway hyperreactivity in allergic asthma models; pharmacological or genetic inhibition of this modification attenuates inflammation and smooth muscle remodelling. Another investigation in a severe equine asthma model demonstrated that combined inhaled corticosteroid and long-acting β2-agonist therapy reverses smooth muscle layer thickening and extracellular matrix deposition in both central and peripheral airways, while reducing neutrophilic inflammation, thereby underscoring the structural normalisation achievable with optimised bronchodilator regimens.

Airway Smooth Muscle Dynamics in Asthma and COPD Pathophysiology publication trend

The graph below shows the total number of articles in airway smooth muscle dynamics in asthma and copd pathophysiology across all publications each year (not limited to Nature Index journals).

Technical terms

Airway smooth muscle (ASM): Contractile cells encircling bronchi that regulate airway calibre through contraction and contribute to remodelling via proliferation and migration.

Airway remodelling: Structural alterations of the airway wall, including smooth muscle hypertrophy, extracellular matrix deposition and epithelial changes, leading to fixed airflow obstruction.

SUMOylation: Post-translational attachment of small ubiquitin-like modifier proteins to target enzymes such as ROCK2, modulating their activity and cellular localisation.

Rho/ROCK signalling: A pathway in which Rho GTPases activate Rho-associated coiled-coil containing kinases, regulating cytoskeletal dynamics, contraction and proliferation.

Long noncoding RNA (lncRNA): Transcripts longer than 200 nucleotides that do not code for protein but regulate gene expression at transcriptional or post-transcriptional levels.

Epithelial–mesenchymal transition (EMT): A process by which epithelial cells acquire mesenchymal characteristics, enhancing motility and contributing to fibrosis and remodelling.

References

1. SUMOylation of Rho-associated protein kinase 2 induces goblet cell metaplasia in allergic airways. Nature Communications (2023).
2. lncRNA CRNDE Affects Th17/IL‐17A and Inhibits Epithelial‐Mesenchymal Transition in Lung Epithelial Cells Reducing Asthma Signs. Oxidative Medicine and Cellular Longevity (2023).
3. Role of Platelet-Derived Growth Factor (PDGF) in Asthma as an Immunoregulatory Factor Mediating Airway Remodeling and Possible Pharmacological Target. Frontiers in Pharmacology (2020).
4. A Role for p38MAPK/HSP27 Pathway in Smooth Muscle Cell Migration*. Journal of Biological Chemistry (1999).
5. Fluticasone/salmeterol reduces remodelling and neutrophilic inflammation in severe equine asthma. Scientific Reports (2017).