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

BMC Pulmonary Medicine

Katri Koli²  Olli Ritvos²  Hongqiang Ma⁴  Outi Leppäranta³  Mikko Rönty²  Eva Sutinen²  Arja Pasternack²  Juha J Hulmi⁵  Jussi Tikkanen²  Marjukka Myllärniemi¹ 

[1] Biomedicum Helsinki C405b, University of Helsinki, PO Box 63, FI-00014 Helsinki, Finland;HUSLAB, Helsinki University Central Hospital, PO Box 400, FI-00029 HUS Helsinki, Finland;Department of Medicine, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, PO Box 63, FI-00014 Helsinki, Finland;Institute of Dentistry, University of Helsinki, PO Box 64, FI-00014 Helsinki, Finland;Department of Biology of Physical Activity, University of Jyväskylä, PO Box 35, Jyväskylä FI-40014, Finland

关键词: Mouse fibrosis model;    Idiopathic pulmonary fibrosis;    Follistatin;    Activins;   

Others  :  1091585
DOI  :  10.1186/1471-2466-14-170

 received in 2014-06-27, accepted in 2014-10-14,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Myllärniemi et al.; licensee BioMed Central Ltd.

【 图 表 】

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