PUBLICAÇÕES científicas

The epidermal growth factor receptor ligand amphiregulin is a negative regulator of hepatic acute-phase gene expression

Ana Pardo-Saganta (1), Maria Ujue Latasa (1), Josefa Castillo (1), Laura Alvarez-Asiain (1), María J. Perugorría (1), Pablo Sarobe (1), Carlos M. Rodriguez-Ortigosa (1), Jesús Prieto (1,2), Carmen Berasain (1), Mónica Santamaría (1)
(1) Division of Hepatology and Gene Therapy, CIMA, University of Navarra, Avda. Pio XII n. 55, 31008 Pamplona, Spain
(2) CiberEhd, Clínica Universidad de Navarra, Pamplona, Spain

Revisão:Journal of Hepatology

Data: 12/Set/2009

Hepatologia

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.

CITAÇÃO DO ARTIGO  J Hepatol. 2009 Dec;51(6):1010-20

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