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

Research Article

Olli Ritvos¹  Arja Pasternack¹  Juha J Hulmi²  Hongqiang Ma³  Outi Leppäranta⁴  Eva Sutinen⁵  Marjukka Myllärniemi⁶  Mikko Rönty⁷  Jussi Tikkanen⁸  Katri Koli⁹ 

[1] Department of Bacteriology and Immunology, Haartman Institute, University of Helsinki, PO Box 21, FI-00014, Helsinki, Finland;HUSLAB, Helsinki University Central Hospital, PO Box 400, FI-00029, Helsinki, HUS, Finland;Department of Biology of Physical Activity, University of Jyväskylä, PO Box 35, FI-40014, Jyväskylä, Finland;Department of Biology of Physical Activity, University of Jyväskylä, PO Box 35, FI-40014, Jyväskylä, Finland;Institute of Dentistry, University of Helsinki, PO Box 64, FI-00014, Helsinki, Finland;Department of Medicine, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, PO Box 63, FI-00014, Helsinki, Finland;Department of Medicine, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, PO Box 63, FI-00014, Helsinki, Finland;HUSLAB, Helsinki University Central Hospital, PO Box 400, FI-00029, Helsinki, HUS, Finland;Department of Medicine, Division of Pulmonary Medicine, University of Helsinki and Helsinki University Central Hospital, PO Box 63, FI-00014, Helsinki, Finland;Transplantation Laboratory, Haartman Institute, University of Helsinki, PO Box 21, FI-00014, Helsinki, Finland;HUSLAB, Helsinki University Central Hospital, PO Box 400, FI-00029, Helsinki, HUS, Finland;Biomedicum Helsinki C405b, University of Helsinki, PO Box 63, FI-00014, Helsinki, Finland;Department of Pathology, Haartman Institute, University of Helsinki, PO Box 21, FI-00014, Helsinki, Finland;HUSLAB, Helsinki University Central Hospital, PO Box 400, FI-00029, Helsinki, HUS, Finland;Transplantation Laboratory, Haartman Institute, University of Helsinki, PO Box 21, FI-00014, Helsinki, Finland;HUSLAB, Helsinki University Central Hospital, PO Box 400, FI-00029, Helsinki, HUS, Finland;Transplantation Laboratory, Haartman Institute, University of Helsinki, PO Box 21, FI-00014, Helsinki, Finland;Research Programs Unit, Translational Cancer Biology, University of Helsinki, PO Box 63, FI-00014, Helsinki, Finland;HUSLAB, Helsinki University Central Hospital, PO Box 400, FI-00029, Helsinki, HUS, Finland;

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

DOI  :  10.1186/1471-2466-14-170

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

来源: Springer

【 摘 要 】

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.

【 授权许可】

CC BY   
© Myllärniemi et al.; licensee BioMed Central Ltd. 2014