The activin A antagonist follistatin inhibits cystic fibrosis-like lung inflammation and pathology

Immunology and Cell Biology
Charles L HardyRobyn E O'Hehir

Abstract

Cystic fibrosis (CF) is the most common life-limiting 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 (β-ENaC) 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 β-ENaC 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 regul...Continue Reading

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Jun 8, 2021·Frontiers in Cell and Developmental Biology·Lingling JiangZhonghui Liu

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Methods Mentioned

BETA
rheology
transgenic
bronchoalveolar lavage
lavages
enzyme-linked immunosorbent assay

Software Mentioned

ImageScope
Graph Pad Prism

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