CUX1/Wnt signaling regulates epithelial mesenchymal transition in EBV infected epithelial cells.
Exp Cell Res
; 315(11): 1819-31, 2009 Jul 01.
Article
en En
| MEDLINE
| ID: mdl-19361498
ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a refractory and lethal interstitial lung disease characterized by alveolar epithelial cells apoptosis, fibroblast proliferation and extra-cellular matrix protein deposition. EBV, localised to alveolar epithelial cells of pulmonary fibrosis patients is associated with a poor prognosis. A strategy based on microarray-differential gene expression analysis to identify molecular drivers of EBV-associated lung fibrosis was utilized. Alveolar epithelial cells were infected with EBV to identify genes whose expression was altered following TGFbeta1-mediated lytic phase. EBV lytic reactivation by TGFbeta1 drives a selective alteration in CUX1 variant (a) (NCBI accession number NM_181552) expression, inducing activation of non-canonical Wnt pathway mediators, implicating it in Epithelial Mesenchymal Transition (EMT), the molecular event underpinning scar production in tissue fibrosis. The role of EBV in EMT can be attenuated by antiviral strategies and inhibition of Wnt signaling by using All-Trans Retinoic Acids (ATRA). Activation of non-canonical Wnt signaling pathway by EBV in epithelial cells suggests a novel mechanism of EMT via CUX1 signaling. These data present a framework for further description of the link between infectious agents and fibrosis, a significant disease burden.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Alveolos Pulmonares
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Proteínas Represoras
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Proteínas Nucleares
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Herpesvirus Humano 4
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Proteínas de Homeodominio
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Proteínas Wnt
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Idioma:
En
Revista:
Exp Cell Res
Año:
2009
Tipo del documento:
Article