Abstract:
BACKGROUND:Activins are members of the TGF-ß superfamily of growth factors. First, we identified by expression array screening that activin-B and follistatin are upregulated in human idiopathic pulmonary fibrosis (IPF). Next, we wanted to clarify their specific role in lung fibrosis formation. METHODS:We used specific antibodies for activin-A and -B subunits and follistatin to measure and localize their levels in idiopathic pulmonary fibrosis and control lung biopsies. To inhibit activin signaling, we used soluble activin type IIB receptor fused to the Fc portion of human IgG1 (sActRIIB-Fc) in two different mouse models of pulmonary fibrosis. RESULTS:Activin-B and follistatin mRNA levels were elevated in the human IPF lung. Immunoreactivity to activin-A, -B and follistatin localized predominantly to the hyperplastic, activated alveolar epithelium, but was also seen in inflammatory cells. Mice treated with sActRIIB-Fc showed increased skeletal muscle mass and a clear reduction in alveolar cell counts in bronchoalveolar lavage fluid, but no significant antifibrotic effect in the lung was observed. CONCLUSIONS:The upregulation of activin-B and follistatin in IPF is a novel finding. Our results indicate that activin inhibition is not an efficient tool for antifibrotic therapy, but could be useful in reducing alveolar cellular response to injury. Activin-B and follistatin levels may be useful as biomarkers of IPF.
journal_name
BMC Pulm Medjournal_title
BMC pulmonary medicineauthors
Myllärniemi M,Tikkanen J,Hulmi JJ,Pasternack A,Sutinen E,Rönty M,Leppäranta O,Ma H,Ritvos O,Koli Kdoi
10.1186/1471-2466-14-170subject
Has Abstractpub_date
2014-11-01 00:00:00pages
170issn
1471-2466pii
1471-2466-14-170journal_volume
14pub_type
杂志文章abstract:BACKGROUND:Chronic obstructive pulmonary disease (COPD) exacerbations are accompanied with increased systemic inflammation, which accelerate the pulmonary function injury and impair the quality of life. Prompt and effective treatments for COPD exacerbations slow down the disease progression, but an objective instrument...
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