Upregulation of activin-B and follistatin in pulmonary fibrosis – a translational study using human biopsies and a specific inhibitor in mouse fibrosis modelsReport as inadecuate




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BMC Pulmonary Medicine

, 14:170

Infectious, Rare and Idiopathic Pulmonary Diseases

Abstract

BackgroundActivins 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.

MethodsWe 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.

ResultsActivin-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.

ConclusionsThe 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.

KeywordsActivins Follistatin Idiopathic pulmonary fibrosis Mouse fibrosis model AbbreviationsALKActivin-like kinase

BALFBronchoalveolar lavage fluid

BMPBone morphogenetic protein

COLCollagen

FSTFollistatin

INHInhibin

IPFIdiopathic pulmonary fibrosis

TGF-ßTransforming growth factor-ß

UIPUsual interstitial pneumonia.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2466-14-170 contains supplementary material, which is available to authorized users.

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Author: Marjukka Myllärniemi - Jussi Tikkanen - Juha J Hulmi - Arja Pasternack - Eva Sutinen - Mikko Rönty - Outi Leppäranta -

Source: https://link.springer.com/







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