Table 1.

Common complete and auxiliary mitogens.

Factor	Origin	Target
Complete mitogens
HGF	Mainly stellate cells	HGF directly regulates hepatocyte DNA synthesis and cell proliferation by blinding to its receptor c-met.
EGF	Brunner's gland in the duodenum	They provoke hepatocyte proliferation mainly through the Ras-MAPK signaling pathway by binding to their identical receptor and may compensate for each other to some degree in the process.
TGF-α	Hepatocytes
Auxiliary mitogens
Bile acids	Hepatocytes and cholangicytes	Appropriate concentration of BAs may promote liver regeneration mainly via farnesoid X receptor (FXR) signaling pathways to stimulate the expression of FoxM1b, a key regulator of cell cycle, to participate in cells proliferation [31].
NE	Nerve system	NE may amplify the effect of EGF and HGF by acting on the α1-adrenergic receptor associated with Gαh, a G protein [32, 33], and besides, it could induced the expression of Smad7 to abolish activin A-induced growth inhibition of hepatocyte by activation of NF-κB [34].
VEGF	Hepatocytes	VEGF family, particularly VEGF-A, is strongly upregulated in hepatocytes during the regenerative process and may facilitate proliferation of sinusoidal endothelial cells and hepatocytes 48 h following PHx [35].
Insulin	Pancreatic islets	Insulin could contribute to liver regeneration despite not being a primary mitogen and its proliferative effect mainly mediated through insulin receptors (IRs) that shift to nucleus to activate inositol 1,4,5,-trisphosphate- (InsP3-) dependent Ca2+ signaling pathways [36].
IGF-1	Liver	IGF-I works as a booster to liver regeneration by upregulation of HGF and downregulation of transforming growth factor beta 1(TGF-β1), a repressor of proliferation, and decreased level of IGF-I could impair the regenerative process [37].
Estrogen	Reproductive system	Estrogen has been shown to promote hepatocyte proliferation mainly through estrogen receptor alpha (ERα) [38]. Moreover, the estrogen level could be influenced by IL-6 and there may be crosstalk between estrogen signaling and IL-6 signaling pathways [39].
Serotonin (5-hydroxytryptamine, 5HT)	Enterochromaffin cells	Serotonin, via HT receptor 2 (HTR2), has been reported to contribute to liver regeneration [40]. And it was found that liver regeneration would be arrested when ketanserin was administrated to block 5-HT2, a subtype of 5-HT, approximately at the G1/S transition point [41].