Copyright ©The Author(s) 2021.
World J Hepatol. Mar 27, 2021; 13(3): 270-290
Published online Mar 27, 2021. doi: 10.4254/wjh.v13.i3.270
Table 1 The main factors driving liver regeneration
Factor of regeneration
Influence on LR
TNF-αInduction of CDK-1
IL-6Activation of the JAK/STAT, MAPK, and PI3K/AKT signaling pathways
Hh signaling pathwayECM remodulation; induction of progenitor cell and liver epithelial cell expansion; induction of glutaminolysis; inhibition of hepatocyte, BEC, Ito cell and progenitor cell apoptosis
ALRlfALR: Enhancement of the hepatocyte response to IL-6 and STAT3 phosphorylation induction. MAPK signaling pathway activation; NK cells inhibition; increase in IL-6, TNFα and iNOS production by Kupffer cells, sfALR: Inhibition of proapoptotic stimuli
NRF2Regulation of M phase entry, hepatocyte proliferation, maintenance of newly formed hepatocytes in a differentiated state
Growth factors (HGF, TGF-α, EGF, HB-EGF)Stimulation of DNA synthesis and cell proliferation via Ras-MAPK and PI3K/AKT signaling pathway activation
BAsActivation of CDK2, cell cycle, regulation of termination phase and terminate liver size, decrease in the inflammatory cytokine production, enhancement of BA excretion and HCO3ˉ, Clˉ secretion, control of BA polarity
Wnt-β-cateninHepatocyte proliferation induction
Notch signaling pathwayModulation of HPC differentiation toward BECs, regulation of hepatocyte proliferation, mitotic rhythms, cyclin E1, A2 and B1
IL-1DNA synthesis inhibitor
SOCSsc-MET and JAK-STAT signaling pathway inhibition
TGF-β1, activin A, BMPsInduction of apoptosis to correct excessive liver mass
HNF4 Regulation of hepatocyte differentiation, initiation of the termination phase, antagonism YAP and TGF-β/SMAD3, prevention of excessive connective tissue synthesis, inhibition of HPC proliferation and migration
Hippo/YAP signaling pathwayTerminal liver size control
Table 2 Main micro ribonucleic acids influencing liver regeneration
Expression change
Target genes
Influence on LR
miR-21IncreasedRhob, Sox7, Crebl2, Bcl-2, Btg2, Timp3, Reck, Pdcd4, Tgfbi, Smad7, PTENInduction
miR -19aIncreasedPTENInduction
miR-503DecreasedCyclin D1, Cyclin E2, CDC25A, CDKN1B, CHK1Suppression
miR-23aDecreasedTNF-α, c-Myc CCNL2, HNF4G METSuppression
miR-150DecreasedTNF-α, survivin, FoxP1, c-MybSuppression
miR-663DecreasedTGF-β1, AP-1, Jun-B, Jun-DSuppression
miR-33DecreasedCDK6, EEF1A1, RAP2ASuppression
miR-26aDecreasedMAP3K2, MXI1, SENP5, CCND2, CCNE2Suppression