Bile acids,FGF15/19 and liver regeneration: From mechanisms to clinical applications |
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Authors: | Gloria Alvarez-Sola Iker Uriarte Maria U Latasa Maddalen Jimenez Marina Barcena-Varela Eva Santamaría Raquel Urtasun Carlos Rodriguez-Ortigosa Jesús Prieto Pedro Berraondo Maite G Fernandez-Barrena Carmen Berasain Matías A Avila |
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Institution: | 1. CIBERehd, Instituto de Salud Carlos III, Clinica Universidad de Navarra, Avda. Pio XII, n 36, 31008 Pamplona, Spain;2. Hepatology Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain;3. Immunology and Immunotherapy Programme, CIMA, Idisna, Universidad de Navarra, Avda, Pio XII, n 55, 31008 Pamplona, Spain |
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Abstract: | 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. |
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Keywords: | Bile acids Fibroblast growth factor 15/19 Liver regeneration |
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