Neurotrophic Factors in Airway Inflammation and Remodeling

Neurotrophic factors, a family of secreted proteins originally characterised for their roles in neuronal survival and growth, have emerged as critical mediators in the pathogenesis of airway inflammation and structural remodelling. Key members, including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3), are expressed by airway epithelial cells, smooth muscle, inflammatory cells and resident immune populations. In inflammatory settings such as asthma, chronic obstructive pulmonary disease and fibrotic lung diseases, neurotrophic factors contribute to neuronal plasticity and neurogenic inflammation, promoting airway hyperresponsiveness through enhanced neurotransmitter release and sensory nerve sprouting. Beyond neural effects, they engage receptors on airway smooth muscle to trigger proliferation and hypertrophy via MAPK and PI3K/Akt pathways, while modulating calcium-handling proteins to augment contractile responses. In parallel, neurotrophic signalling influences dendritic cell maturation and T-helper type 2 polarisation, thereby sustaining allergic inflammation. Overproduction of these factors can lead to extracellular matrix deposition, subepithelial fibrosis and irreversible changes in airway calibre. Experimental inhibition of NGF or blockade of tropomyosin-related kinase (Trk) receptors has been shown to attenuate remodelling features in preclinical models, highlighting their potential as therapeutic targets. The pleiotropic actions of neurotrophic factors at the interface of the nervous, immune and structural compartments underscore their global significance in airway disease and open avenues for targeted interventions aimed at both inflammation and remodelling.

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Neurotrophic Factors in Airway Inflammation and Remodeling publication trend

The graph below shows the total number of articles in neurotrophic factors in airway inflammation and remodeling across all publications each year (not limited to Nature Index journals).

Technical terms

Neurotrophic factors: Secreted proteins that support neuronal growth but also modulate immune and structural cells in the airway.

Airway remodelling: Structural alteration of the airway wall, including smooth muscle hypertrophy, subepithelial fibrosis and extracellular matrix deposition.

Trk receptors: High-affinity tropomyosin-related kinase receptors (TrkA, TrkB, TrkC) that mediate neurotrophic signalling.

Neurogenic inflammation: Inflammatory response driven by sensory nerve activation and neuropeptide release.

Airway hyperresponsiveness: Exaggerated constrictive response of the airway smooth muscle to stimuli.

References

1. Nerve Growth Factor: A Potential Therapeutic Target for Lung Diseases. International Journal of Molecular Sciences (2021).
2. Brain‐derived neurotrophic factor induces proliferation of human airway smooth muscle cells. Journal of Cellular and Molecular Medicine (2012).
3. Lung dendritic cells undergo maturation and polarization towards a T helper type 2-stimulating phenotype in a mouse model of asthma: Role of nerve growth factor. Experimental and Therapeutic Medicine (2014).
4. Up-regulation of systemic and local BDNF in non-allergic Nasal Polyps in China. Pakistan Journal of Medical Sciences (2024).
5. Brain-Derived Neurotrophic Factor Enhances Calcium Regulatory Mechanisms in Human Airway Smooth Muscle. PLOS ONE (2012).