14 December 2020: Review Articles
Cell Sources and Influencing Factors of Liver Regeneration: A Review
Chengzhan Zhu 12AEG , Bingzi Dong 2FG , Leqi Sun 3EF , Yixiu Wang 1BCE , Shuhai Chen 4AEF*DOI: 10.12659/MSM.929129
Med Sci Monit 2020; 26:e929129
Table 1 The molecules involved in liver regeneration.
| Function | Molecule | Mechanism | Source | Year | Refs |
|---|---|---|---|---|---|
| Positive | ARF6 | Stimulated by HGF, ARF6 can help to recruit PIP5K1A into c-Met and activate the PIP2-PIP3-AKT pathway | MouseHuman cell line | 2017 | []21 |
| LASS2 | Lass2 gene knockout may result in the lack of fatty acids in hepatocytes and AKT phosphorylation, which can lead to hepatocyte hypertrophy to block liver regeneration | Mouse | 2017 | []22 | |
| LKB1 | Master kinase LKB1 can regulate the EGFR signal to regulate the cell cycle. LKB1 controls the fidelity of mitosis to modulate the hepatocyte ploidy in the LR process | Mouse | 2018 | []23 | |
| IPMK | IPMK-AMPK-Sirt-1 and IPMK-AMPK-ULK1 are 2 autophagy pathways. IPMK deletion abolishes lipophagy and impairs hepatocyte regeneration | Mouse | 2019 | []24 | |
| miR-21 | Upregulates cyclin-D1 and accelerates the G1/S phase transition of hepatocytes | Mouse | 2016 | []25 | |
| miR-10a | Downregulates the EphA4 to increase the percentage of S phase and G2/M phase cells | Rat | 2018 | []26 | |
| Exosome | Hepatocyte-derived exosome can directly fuse with the hepatocytes, transfer neutral ceramidase and SK2, and promote SLP synthesis to enhance LR | Mouse | 2016 | []27 | |
| Nrf2 | ROS induces Nrf2 dissociation from the Keap1-Nrf2 complex and transfers to nuclei to regulate the gene transcription of cell proliferation. The appropriate amount of Nrf2 can regulate HNF4α, AKT1, and p70s6k to promote the complete differentiation of the newly regenerating hepatocytes after PH | Mouse | 2015 | []28 | |
| Nrf2 is also involved in HPC-mediated LR under a chronic liver disease background | Mouse | 2019 | []29 | ||
| Baicalin induces Nrf2 accumulation in cytoplasm leads to NLRP3 inflammasome activation and increases expression of IL-18, which induces hepatocytes proliferation | Mouse | 2020 | []30 | ||
| Negative | Nrf2 | Excessive activation of Nrf2 can delay proliferation and induce apoptosis of hepatocytes in the regenerating liver through targeting p15 and Bcl2l11 genes | Mouse | 2014 | []31 |
| Tmub1 | Interacts with cyclin A2 during the cell cycle, and the overexpression of Tmub1 may postpone cyclin A2 and cyclin B1 degradation in the M phase | Rat | 2018 | []32 | |
| Tmub1 can be downregulated by miR-27a/b to regulate hepatocyte proliferation | RatHuman cell line | 2018 | []33 | ||
| Tmub1 negatively regulates liver regeneration by inhibiting STAT3 phosphorylation | MouseHuman cell line | 2019 | []34 | ||
| PTEN | Myeloid PTEN deficiency changes Kupffer cell phenotype after PH, which thereby leads to reduced NK cell activity, decreases the release of liver regeneration inhibitor IFN-γ. Kupffer cell also increases the release of growth factors (HGF, OSM) to promoting LR | Mouse | 2017 | []35 | |
| After hepatectomy, PTEN downregulation can promote the utilization of TRAS, and transform the resting synthetic metabolic function into catabolic activity in the case of tissue loss, thereby enhancing liver regeneration | Mouse | 2017 | []36 | ||
| ALR can induce miR-26a expression to downregulate PTEN, and promote hepatocyte proliferation through the P-AKT/cyclin D1 pathway | RatHuman cell linePatient sample | 2019 | []37 | ||
| miR-34a | Targets the Notch receptor, Bcl-2, and Bcl-xL, arrests cell cycle mainly in the G2/M phase, and increases cell apoptosis rate | Mouse | 2017 | []38 | |
| ARF6 – ADP-ribosylation factor 6; LASS2 – homo sapiens longevity assurance homolog 2 of yeast LAG1; IPMK – inositol polyphosphate multikinase; LKB1 – liver kinase B1; miRNAs – microRNAs; NLRP3 – NOD-like receptor pyrin domain containing; Nrf2 – nuclear factor erythroid-2-related factor 2; OSM – oncostatin M; PTEN – phosphate and tension homology deleted on chromosome 10; SK2 – sphingosine kinase 2; SLP – sphingosine-1-phosphate; Tmub1 – transmembrane and ubiquitin-like domain-containing protein 1; TRAS – transient regeneration-associated steatosis. | |||||