The activin A antagonist follistatin inhibits asthmatic airway remodelling

Hardy, C, Nguyen, H, Mohamud, R, Yao, J, Oh, D, Plebanski, M, Loveland, K, Harrison, C, Rolland, J and O'Hehir, R 2013, 'The activin A antagonist follistatin inhibits asthmatic airway remodelling', Thorax, vol. 68, no. 1, pp. 9-18.

Document type: Journal Article
Collection: Journal Articles

Title The activin A antagonist follistatin inhibits asthmatic airway remodelling
Author(s) Hardy, C
Nguyen, H
Mohamud, R
Yao, J
Oh, D
Plebanski, M
Loveland, K
Harrison, C
Rolland, J
O'Hehir, R
Year 2013
Journal name Thorax
Volume number 68
Issue number 1
Start page 9
End page 18
Total pages 10
Publisher B M J Group
Abstract Background: Current pharmacotherapy is highly effective in the clinical management of the majority of patients with stable asthma, however severe asthma remains inadequately treated. Prevention of airway remodelling is a major unmet clinical need in the management of patients with chronic severe asthma and other inflammatory lung diseases. Accumulating evidence convincingly demonstrates that activin A, a member of the transforming growth factor (TGF)-β superfamily, is a key driver of airway inflammation, but its role in chronic asthmatic airway remodelling is ill-defined. Follistatin, an endogenously produced protein, binds activin A with high affinity and inhibits its bioactivity. The aim of this study was to test the potential of follistatin as a therapeutic agent to inhibit airway remodelling in an experimental model of chronic allergic airway inflammation. Methods: BALB/c mice were systemically sensitised with ovalbumin (OVA), and challenged with OVA intranasally three times a week for 10 weeks. Follistatin was instilled intranasally during allergen challenge. Results: Chronic allergen challenge induced mucus hypersecretion and subepithelial collagen deposition which persisted after cessation of challenge. Intranasal follistatin (0.05, 0.5, 5 µg) inhibited the airway remodelling and dose-dependently decreased airway activin A and TGF-β1, and allergen-specific T helper 2 cytokine production in the lung-draining lymph nodes. Follistatin also impaired the loss of TGF-β1 and activin RIB immunostaining in airway epithelium which occurred following chronic allergen challenge. Conclusions: These data demonstrate that follistatin attenuates asthmatic airway remodelling. Our findings point to the potential of follistatin as a therapeutic for prevention of airway remodelling in asthma and other inflammatory lung diseases.
Subject Immunology not elsewhere classified
DOI - identifier 10.1136/thoraxjnl-2011-201128
Copyright notice © 2013 BMJ Publishing Group Limited.
ISSN 0040-6376
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