Upregulation of activin-B and follistatin in pulmonary fibrosis: a translational study using human biopsies and a specific inhibitor in mouse fibrosis models
| Autor: | Hongqiang Ma, Arja Pasternack, Katri Koli, Olli Ritvos, Jussi Tikkanen, Juha J. Hulmi, Outi Leppäranta, Marjukka Myllärniemi, Mikko Rönty, Eva Sutinen |
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| Přispěvatelé: | Clinicum, Department of Medicine, Keuhkosairauksien yksikkö, Transplantation Laboratory, Haartman Institute (-2014), Department of Bacteriology and Immunology, Department of Pathology, Department of Oral and Maxillofacial Diseases, Research Programs Unit, Growth factor physiology |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
Pathology Follistatin Pulmonary Fibrosis PROTEIN Cell Count Quadriceps Muscle ACTIVATION Idiopathic pulmonary fibrosis Mice BMP-7 Fibrosis Pulmonary fibrosis follistatin Inhibin-beta Subunits GREMLIN Immunity Cellular medicine.diagnostic_test biology activins PIRFENIDONE Pirfenidone respiratory system idiopathic pulmonary fibrosis Mouse fibrosis model 3. Good health Up-Regulation Activins medicine.anatomical_structure ACUTE EXACERBATION mouse fibrosis model embryonic structures GROWTH Bronchoalveolar Lavage Fluid hormones hormone substitutes and hormone antagonists medicine.drug Research Article Signal Transduction Pulmonary and Respiratory Medicine EXPRESSION medicine.medical_specialty endocrine system Recombinant Fusion Proteins education Respiratory Mucosa Alveolar cells INFLAMMATION medicine Animals Humans RNA Messenger Lung business.industry medicine.disease respiratory tract diseases Mice Inbred C57BL Pulmonary Alveoli Disease Models Animal Bronchoalveolar lavage Protein Biosynthesis 3121 General medicine internal medicine and other clinical medicine biology.protein business |
| Zdroj: | BMC Pulmonary Medicine |
| Popis: | 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. peerReviewed |
| Databáze: | OpenAIRE |
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