BARD1 mediates TGF-ß signaling in pulmonary fibrosis.
Respir Res
; 16: 118, 2015 Sep 29.
Article
en En
| MEDLINE
| ID: mdl-26415510
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-ß signaling, both recognized factors driving lung fibrosis. Differentially spliced BARD1 isoforms, in particular BARD1ß, 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-ß in cultured cells, in mice with experimentally induced lung fibrosis, and in lung biopsies from pulmonary fibrosis patients.RESULTS:
FL BARD1 and BARD1ß were upregulated in response to TGF-ß 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 BARD1ß in fibrotic tissues.CONCLUSION:
Our data suggest that FL BARD1 and BARD1ß might be mediators of pleiotropic effects of TGF-ß. In particular BARD1ß might be a driver of proliferation and of pulmonary fibrosis pathogenesis and progression and represent a target for treatment.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Supresoras de Tumor
/
Ubiquitina-Proteína Ligasas
/
Factor de Crecimiento Transformador beta1
/
Fibrosis Pulmonar Idiopática
/
Pulmón
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Respir Res
Año:
2015
Tipo del documento:
Article
País de afiliación:
Suiza