TGF-β Signaling in Airway Inflammation and Remodeling

Transforming growth factor-β (TGF-β) is a pleiotropic cytokine central to the orchestration of inflammatory responses and structural changes within the airways. Upon release by epithelial cells, fibroblasts, inflammatory leukocytes and smooth muscle, TGF-β engages cell surface receptors to activate canonical Smad-dependent signalling as well as diverse non-Smad cascades. In the airways, TGF-β drives subepithelial fibrosis, myofibroblast differentiation and extracellular matrix deposition, contributing to thickening of the airway wall and loss of functional elasticity. Concurrently, it modulates immune cell recruitment and differentiation, balancing pro- and anti-inflammatory programmes. Dysregulated TGF-β activity underpins the pathological remodelling observed in asthma and chronic obstructive pulmonary disease, promoting epithelial-to-mesenchymal transition, smooth muscle hypertrophy and mucus hypersecretion. Cross-talk with pathways such as Wnt/β-catenin and MAP kinases amplifies profibrotic signals, while interaction with regulatory proteins including kinases and isomerases fine-tunes cytokine production. A deeper understanding of the receptor subtypes, intracellular mediators and context-dependent effects of TGF-β has revealed potential targets for therapeutic modulation, with the aim of restraining airway fibrosis without compromising essential repair processes.

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TGF-β Signaling in Airway Inflammation and Remodeling publication trend

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

Technical terms

Transforming growth factor-β (TGF-β): A cytokine that regulates cell proliferation, differentiation, extracellular matrix production and immune responses.

Smad pathway: Canonical intracellular signalling cascade activated by TGF-β receptors, involving Smad2/3/4 proteins that translocate to the nucleus to regulate gene transcription.

Airway remodeling: Structural alterations in the bronchial wall, including fibrosis, smooth muscle hypertrophy and mucus gland hyperplasia, leading to impaired airway function.

Epithelial-to-mesenchymal transition (EMT): A process by which epithelial cells acquire mesenchymal characteristics, contributing to fibroblast accumulation and matrix deposition.

β-catenin/TCF complex: A key effector of Wnt signalling that partners with TCF transcription factors; modulating its activity can influence TGF-β-driven profibrotic programmes.

References

1. TGF-β, IL-1β, IL-6 levels and TGF-β/Smad pathway reactivity regulate the link between allergic diseases, cancer risk, and metabolic dysregulations. Frontiers in Immunology (2024).
2. The Role of Transforming Growth Factor-β (TGF-β) in Asthma and Chronic Obstructive Pulmonary Disease (COPD). Cells (2024).
3. TGF-β-Activated Kinase 1 (TAK1) Signaling Regulates TGF-β-Induced WNT-5A Expression in Airway Smooth Muscle Cells via Sp1 and β-Catenin. PLOS ONE (2014).
4. Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1. Therapeutic Advances in Respiratory Disease (2021).