The liver is unique in regenerative potential, which could recover the lost mass and function after injury from ischemia and resection. The underlying molecular mechanisms of liver regeneration have been extensively studied in the past using the partial hepatectomy (PH) model in rodents, where 2/3 PH is carried out by removing two lobes. The whole process of liver regeneration is complicated, orchestrated event involving a network of connected interactions, which still remain fully elusive. Bile acids (BAs) are ligands of farnesoid X receptor (FXR), a nuclear receptor of ligand-activated transcription factor. FXR has been shown to be highly involved in liver regeneration. BAs and FXR not only interact with each other but also regulate various downstream targets independently during liver regeneration. Moreover, recent findings suggest that tissue-specific FXR also contributes to liver regeneration significantly. These novel findings suggest that FXR has much broader role than regulating BA, cholesterol, lipid and glucose metabolism. Therefore, these researches highlight FXR as an important pharmaceutical target for potential use of FXR ligands to regulate liver regeneration in clinic. This review focuses on the roles of BAs and FXR in liver regeneration and the current underlying molecular mechanisms which contribute to liver regeneration.
Keywords: ABC, ATP-binding cassette; AMPK, AMP-activated protein kinase; BA, bile acid; Bile acids; C/EBPβ, CCAAT-enhancer binding protein β; CA, cholic acid; CDCA, chenodeoxycholic acid; CTX, cerebrotendinous xanthomatosis; CYP7A1, cholesterol 7alpha-hydroxylase; CYP8B1, sterol 12α-hydroxylase; Cyp27-KO, sterol 27-hydroxylase–knockout; DDAH-1, dimethylarginineaminohydrolase-1; ERK1/2, extracellular signal-regulated kinase 1/2; FGF-15, fibroblast growth factor 15; FGFR4, FGF receptor 4; FOXM1b, forkhead boxm1b; FXR, farnesoid X receptor; Farnesoid X receptor; Fibroblast growth factor 15; Fxr-KO, Fxr-knockout; GPBAR1 or TGR5, G protein-coupled BA receptor 1; HEX, hematopoietically expressed homeobox; JNK, c-Jun N-terminal kinase; KC, Kupffer cells; KO, knockout; Liver regeneration; Liver-intestine croass talk; MAPK, mitogen-activated protein kinase; MRP3, multidrug resistance associated protein 3; NASH, nonalcoholic steatohepatitis; NF-κB, nuclear factor-κB; PH, partial hepatectomy; Rb, retinoblastoma; SHP, small heterodimer partner; STAT3, signal transducer and activator of transcription 3; TH, thyroid hormone; THR, TH receptor; Transmembrane G protein coupled receptor 5; WT, wild type; cAMP, cyclic adenosine monophosphate; hepFxr-KO, hepatocyte-specific Fxr knockout.