RT Journal Article
SR Electronic
T1 The activin A antagonist follistatin inhibits asthmatic airway remodelling
JF Thorax
JO Thorax
FD BMJ Publishing Group Ltd and British Thoracic Society
SP 9
OP 18
DO 10.1136/thoraxjnl-2011-201128
VO 68
IS 1
A1 Charles Linton Hardy
A1 Hong-An Nguyen
A1 Rohimah Mohamud
A1 John Yao
A1 Ding Yuan Oh
A1 Magdalena Plebanski
A1 Kate L Loveland
A1 Craig A Harrison
A1 Jennifer M Rolland
A1 Robyn E O'Hehir
YR 2013
UL http://thorax.bmj.com/content/68/1/9.abstract
AB 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.