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RESEARCH PRODUCT
Upregulation of activin-B and follistatin in pulmonary fibrosis: a translational study using human biopsies and a specific inhibitor in mouse fibrosis models
Hongqiang MaHongqiang MaArja PasternackArja PasternackKatri KoliKatri KoliOlli RitvosOlli RitvosJussi TikkanenJussi TikkanenJuha J. HulmiOuti LeppärantaMarjukka MyllärniemiMikko RöntyMikko RöntyEva Sutinensubject
MalePathologyFollistatinPulmonary FibrosisPROTEINCell CountQuadriceps MuscleACTIVATIONIdiopathic pulmonary fibrosisMiceBMP-7FibrosisPulmonary fibrosisfollistatinInhibin-beta SubunitsGREMLINImmunity Cellularmedicine.diagnostic_testbiologyactivinsPIRFENIDONEPirfenidonerespiratory systemidiopathic pulmonary fibrosisMouse fibrosis model3. Good healthUp-RegulationActivinsmedicine.anatomical_structureACUTE EXACERBATIONmouse fibrosis modelembryonic structuresGROWTHBronchoalveolar Lavage Fluidhormones hormone substitutes and hormone antagonistsmedicine.drugResearch ArticleSignal TransductionPulmonary and Respiratory MedicineEXPRESSIONmedicine.medical_specialtyendocrine systemRecombinant Fusion ProteinseducationIdiopathic pulmonary fibrosisRespiratory MucosaAlveolar cellsINFLAMMATIONmedicineAnimalsHumansRNA MessengerLungbusiness.industrymedicine.diseaserespiratory tract diseasesMice Inbred C57BLPulmonary AlveoliDisease Models AnimalBronchoalveolar lavageProtein Biosynthesis3121 General medicine internal medicine and other clinical medicinebiology.proteinbusinessFollistatindescription
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
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2014-11-01 |