Review
Copyright ©2014 Baishideng Publishing Group Inc.
World J Gastroenterol. Nov 21, 2014; 20(43): 16167-16177
Published online Nov 21, 2014. doi: 10.3748/wjg.v20.i43.16167
Table 1 Sum-up of signal molecules involved in liver regeneration
Regeneration PhasesMolecular factorsOriginTargets and EffectsInvolved Signalling pathways
Priming stageNitric oxide, prostaglandins, tumor necrosis factor, interleukin 6NPLCsTrigger of liver regeneration, sensitizing hepatocytes to growth factors for replicationNF-κB, JAK/STAT3 and MAPK signaling pathway
Proliferation stageHGFHSCs and other NPLCs, hepatocytes; mesenchymal cellsCooperative effects allow the hepatocytes to overcome cell-cycleHGF/cMet signaling pathway
TGF-αHepatocytes, HSCsCheckpoint-controls and transition of hepatocytes from G0, through G1, to the S phase of the cell cycle, leading to DNA synthesis and cell proliferationEGFR signaling pathway IGF-1R and insulin receptor
EGFSalivary glands in intestine and pancreas
IGFHepatocytes, NPLCs
PDGFHepatocytesMitosis in NPLCs, remodelling of ECMPDGFR in HSCs
VEGFVEGF receptor in endothelial cells
Termination stageTGF-βHSCs, other NPLCs, mesenchymal cellsInhibition of hepatocyte DNA synthesis, remodeling of ECM, restoration at the end of regenerationTGF-β signaling pathway
OthersWnt/β-catenin plays a supportive role in liver regeneration; metalloproteinase play a pivotal role in ECM degradation, generation and degradation of active growth factor and signaling molecules in the ECM