Journal article
BARD1 mediates TGF-β signaling in pulmonary fibrosis
Respiratory Research, Vol.16(1), Art. 118
2015
Abstract
Background
Idiopathic pulmonary fibrosis (IPF) is a rapid progressive fibro-proliferative disorder with poor prognosis similar to lung cancer. The pathogenesis of IPF is uncertain, but loss of epithelial cells and fibroblast proliferation are thought to be central processes. Previous reports have shown that BARD1 expression is upregulated in response to hypoxia and associated with TGF-β signaling, both recognized factors driving lung fibrosis. Differentially spliced BARD1 isoforms, in particular BARD1β, are oncogenic drivers of proliferation in cancers of various origins. We therefore hypothesized that BARD1 and/or its isoforms might play a role in lung fibrosis.
Methods
We investigated BARD1 expression as a function of TGF-β in cultured cells, in mice with experimentally induced lung fibrosis, and in lung biopsies from pulmonary fibrosis patients.
Results
FL BARD1 and BARD1β were upregulated in response to TGF-β in epithelial cells and fibroblasts in vitro and in vivo. Protein and mRNA expression studies showed very low expression in healthy lung tissues, but upregulated expression of full length (FL) BARD1 and BARD1β in fibrotic tissues.
Conclusion
Our data suggest that FL BARD1 and BARD1β might be mediators of pleiotropic effects of TGF-β. In particular BARD1β might be a driver of proliferation and of pulmonary fibrosis pathogenesis and progression and represent a target for treatment.
Details
- Title
- BARD1 mediates TGF-β signaling in pulmonary fibrosis
- Authors/Creators
- P-A André (Author/Creator) - Geneva CollegeC.M. Prêle (Author/Creator) - Harry Perkins Institute of Medical ResearchS. Vierkotten (Author/Creator) - Comprehensive Pneumology Center, Ludwig-Maximilians-University, University hospital Grosshadern, and Helmholtz Zentrum München, Munich, GermanyS. Carnesecchi (Author/Creator) - University Hospital of GenevaY. Donati (Author/Creator) - University Hospital of GenevaR.C. Chambers (Author/Creator) - Centre for Inflammation and Tissue Repair University College London London UKJ-C Pache (Author/Creator) - Department of Clinical Pathology Geneva University Hospitals Geneva SwitzerlandB. Crestani (Author/Creator) - Délégation Paris 7C. Barazzone-Argiroffo (Author/Creator) - University Hospital of GenevaM. Konigshoff (Author/Creator) - Comprehensive Pneumology Center, Ludwig-Maximilians-University, University hospital Grosshadern, and Helmholtz Zentrum München, Munich, GermanyG.J. Laurent (Author/Creator) - Harry Perkins Institute of Medical ResearchI. Irminger-Finger (Author/Creator) - Harry Perkins Institute of Medical Research
- Publication Details
- Respiratory Research, Vol.16(1), Art. 118
- Publisher
- BioMed Central
- Identifiers
- 991005540045507891
- Copyright
- © 2015 André et al.
- Murdoch Affiliation
- Murdoch University
- Language
- English
- Resource Type
- Journal article
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Source: InCites
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.208 Vasculitis & Autoimmune Disorders
- 1.208.1262 Idiopathic Pulmonary Fibrosis
- Web Of Science research areas
- Respiratory System
- ESI research areas
- Clinical Medicine