The activin A antagonist follistatin inhibits asthmatic airway remodelling

Charles Linton Hardy, Hong-An Thi Nguyen, Rohimah Mohamud, Jun John Yao, Ding Yuan Oh, Magdalena Plebanski, Katherine Ann Lakoski Loveland, Craig Harrison, Jennifer May Rolland, Robyn E O'Hehir

Research output: Contribution to journalArticleResearchpeer-review

36 Citations (Scopus)

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)-?? 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 I?g) inhibited the airway remodelling and dose-dependently decreased airway activin A and TGF-??1, and allergen-specific T helper 2 cytokine production in the lung-draining lymph nodes. Follistatin also impaired the loss of TGF-??1 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. Copyright Article author (or their employer) 2012.
Original languageEnglish
Pages (from-to)9 - 18
Number of pages10
JournalThorax
Volume68
Issue number1
DOIs
Publication statusPublished - 2013

Cite this