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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Terapia génica y Hepatología > Inmunología experimental > DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista >

The epidermal growth factor receptor ligand amphiregulin is a negative regulator of hepatic acute-phase gene expression
Authors: Pardo-Saganta, A. (Ana)
Latasa, M.U. (María Ujué)
Castillo, J. (Josefa)
Alvarez-Asiain, L. (Laura)
Perugorria, M.J. (María J.)
Sarobe, P. (Pablo)
Rodriguez-Ortigosa, C.M. (Carlos M.)
Prieto, J. (Jesús)
Berasain, C. (Carmen)
Santamaria, M. (Mónica)
Avila, M.A. (Matías Antonio)
Keywords: Acute-phase proteins
Amphiregulin
Oncostatin
Liver regeneration
Issue Date: 2009
Publisher: Elsevier
Publisher version: http://www.sciencedirect.com/science/article/pii/S0168827809005820
ISSN: 1600-0641
Citation: Pardo-Saganta A, Latasa MU, Castillo J, Alvarez-Asiain L, Perugorria MJ, Sarobe P, et al. The epidermal growth factor receptor ligand amphiregulin is a negative regulator of hepatic acute-phase gene expression. J Hepatol 2009 Dec;51(6):1010-1020.
Abstract
BACKGROUND/AIMS: The modulation of the hepatic acute-phase reaction (APR) that occurs during inflammation and liver regeneration is important for allowing normal hepatocellular proliferation and the restoration of homeostasis. Activation of acute-phase protein (APP) gene expression by interleukin-6 (IL-6)-type cytokines is thought to be counteracted by growth factors released during hepatic inflammation and regeneration. The epidermal growth factor receptor (EGFR) ligand amphiregulin (AR) is readily induced by inflammatory signals and plays a nonredundant protective role during liver injury. In this paper, we investigated the role of AR as a modulator of liver APP gene expression. METHODS: Expression of APP genes was measured in the livers of AR(+/+) and AR(-/-)mice during inflammation and regeneration and in cultured liver cells treated with AR and oncostatin M (OSM). Crosstalk between AR and OSM signalling was studied. RESULTS: APP genes were overexpressed in the livers of AR(-/-) mice during inflammation and hepatocellular regeneration. In cultured AR-null hepatocytes and human hepatocellular carcinoma (HCC) cells after AR knockdown, APP gene expression is enhanced. AR counteracts OSM-triggered signal transducer and activator of transcription 3 signalling in hepatocytes and attenuates APP gene transcription. CONCLUSIONS: Our data support the relevance of EGFR-mediated signalling in the modulation of cytokine-activated pathways. We have identified AR as a key regulator of hepatic APP gene expression during inflammation and liver regeneration.
Permanent link: http://hdl.handle.net/10171/21665
Appears in Collections:DA - CIMA - Servicios de apoyo - Instalación radioactiva - Artículos
DA - CIMA - Terapia génica y Hepatología - Oncobiología - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Hepatología experimental - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Hepatología bioquímica - Artículos de revista
DA - Medicina - Medicina Interna - Artículos de revista
DA - CIMA - Terapia génica y Hepatología - Inmunología experimental - Artículos de revista

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