Portal de Periódicos da CAPES

Bile acids, FGF15/19 and liver regeneration: From mechanisms to clinical applications

2017; Elsevier BV; Volume: 1864; Issue: 4 Linguagem: Inglês

10.1016/j.bbadis.2017.06.025

1879-260X

Gloria Álvarez‐Sola, Iker Uriarte, María U. Latasa, Maddalen Jiménez, Marina Bárcena‐Varela, Eva Santamaría, Raquel Urtasun, Carlos M. Rodríguez‐Ortigosa, Jesús Prìeto, Pedro Berraondo, Maite G. Fernández‐Barrena, Carmen Berasain, Matías A. Ávila,

Genetic and Kidney Cyst Diseases

The liver has an extraordinary regenerative capacity rapidly triggered upon injury or resection. This response is intrinsically adjusted in its initiation and termination, a property termed the "hepatostat". Several molecules have been involved in liver regeneration, and among them bile acids may play a central role. Intrahepatic levels of bile acids rapidly increase after resection. Through the activation of farnesoid X receptor (FXR), bile acids regulate their hepatic metabolism and also promote hepatocellular proliferation. FXR is also expressed in enterocytes, where bile acids stimulate the expression of fibroblast growth factor 15/19 (FGF15/19), which is released to the portal blood. Through the activation of FGFR4 on hepatocytes FGF15/19 regulates bile acids synthesis and finely tunes liver regeneration as part of the "hepatostat". Here we review the experimental evidences supporting the relevance of the FXR-FGF15/19-FGFR4 axis in liver regeneration and discuss potential therapeutic applications of FGF15/19 in the prevention of liver failure. This article is part of a Special Issue entitled: Cholangiocytes in Health and Disease edited by Jesus Banales, Marco Marzioni, Nicholas LaRusso and Peter Jansen.