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Background

Liver regeneration following partial hepatectomy (PHx) is a complicated process involving multiple organs and several types of signaling networks. The bile acid-activated metabolic pathways occupy an auxiliary yet important chapter in the entire biochemical story. PHx is characterized by rapid but transient bile acid overload in the liver, which constitutes the first wave of proliferative signaling in the remnant hepatocytes. Bile acids trigger hepatocyte proliferation through activation of several nuclear receptors. Following biliary passage into the intestines, enterocytes reabsorb the bile acids, which results in the activation of farnesoid X receptor (FXR), the consequent excretion of fibroblast growth factor (FGF) 19/FGF15, and its release into the enterohepatic circulation. FGF19/FGF15 subsequently binds to its cognate receptor, fibroblast growth factor receptor 4 (FGFR4) complexed with β-klotho, on the …