{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T04:21:26Z","timestamp":1764044486991},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T00:00:00Z","timestamp":1425945600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"funder":[{"name":"NHMRC Australia"},{"name":"CASS Foundation and Paranta Biosciences, Australia"},{"name":"Victorian Government's Operational"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Immunol Cell Biol"],"published-print":{"date-parts":[[2015,7]]},"abstract":"<jats:p>Cystic fibrosis (CF) is the most common life\u2010limiting genetically acquired respiratory disorder. Patients with CF have thick mucus obstructing the airways leading to recurrent infections, bronchiectasis and neutrophilic airway inflammation culminating in deteriorating lung function. Current management targets airway infection and mucus clearance, but despite recent advances in care, life expectancy is still only 40 years. We investigated whether activin A is elevated in CF lung disease and whether inhibiting activin A with its natural antagonist follistatin retards lung disease progression. We measured serum activin A levels, lung function and nutritional status in CF patients. We studied the effect of activin A on CF lung pathogenesis by treating newborn CF transgenic mice (\u03b2\u2010ENaC) intranasally with the natural activin A antagonist follistatin. Activin A levels were elevated in the serum of adult CF patients, and correlated inversely with lung function and body mass index. Follistatin treatment of newborn \u03b2\u2010ENaC mice, noted for respiratory pathology mimicking human CF, decreased the airway activin A levels and key features of CF lung disease including mucus hypersecretion, airway neutrophilia and levels of mediators that regulate inflammation and chemotaxis. Follistatin treatment also increased body weight and survival of \u03b2\u2010ENaC mice, with no evidence of local or systemic toxicity. Our findings demonstrate that activin A levels are elevated in CF and provide proof\u2010of\u2010concept for the use of the activin A antagonist, follistatin, as a therapeutic in the long\u2010term management of lung disease in CF patients.<\/jats:p>","DOI":"10.1038\/icb.2015.7","type":"journal-article","created":{"date-parts":[[2015,3,10]],"date-time":"2015-03-10T10:36:06Z","timestamp":1425983766000},"page":"567-574","source":"Crossref","is-referenced-by-count":27,"title":["The activin A antagonist follistatin inhibits cystic fibrosis\u2010like lung inflammation and pathology"],"prefix":"10.1111","volume":"93","author":[{"given":"Charles L","family":"Hardy","sequence":"first","affiliation":[{"name":"Department of Allergy, Immunology &amp; Respiratory Medicine, Central Clinical School, Monash University  Melbourne Victoria Australia"},{"name":"Department of Immunology, Central Clinical School, Monash University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susannah J","family":"King","sequence":"additional","affiliation":[{"name":"Department of Allergy, Immunology &amp; Respiratory Medicine, The Alfred Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole A","family":"Mifsud","sequence":"additional","affiliation":[{"name":"Department of Allergy, Immunology &amp; Respiratory Medicine, Central Clinical School, Monash University  Melbourne Victoria Australia"},{"name":"Department of Allergy, Immunology &amp; Respiratory Medicine, The Alfred Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark P","family":"Hedger","sequence":"additional","affiliation":[{"name":"MIMR\u2010PHI Institute of Medical Research  Clayton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J","family":"Phillips","sequence":"additional","affiliation":[{"name":"MIMR\u2010PHI Institute of Medical Research  Clayton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabienne","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Immunology, Central Clinical School, Monash University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David M","family":"de Kretser","sequence":"additional","affiliation":[{"name":"MIMR\u2010PHI Institute of Medical Research  Clayton Victoria Australia"},{"name":"Department of Anatomy and Developmental Biology, Monash University  Clayton Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John W","family":"Wilson","sequence":"additional","affiliation":[{"name":"Department of Allergy, Immunology &amp; 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