Logo Medical Science Monitor

Call: +1.631.470.9640
Mon - Fri 10:00 am - 02:00 pm EST

Contact Us

Logo Medical Science Monitor Logo Medical Science Monitor Logo Medical Science Monitor

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.

PositiveARF6Stimulated by HGF, ARF6 can help to recruit PIP5K1A into c-Met and activate the PIP2-PIP3-AKT pathwayMouseHuman cell line2017[]21
LASS2Lass2 gene knockout may result in the lack of fatty acids in hepatocytes and AKT phosphorylation, which can lead to hepatocyte hypertrophy to block liver regenerationMouse2017[]22
LKB1Master 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 processMouse2018[]23
IPMKIPMK-AMPK-Sirt-1 and IPMK-AMPK-ULK1 are 2 autophagy pathways. IPMK deletion abolishes lipophagy and impairs hepatocyte regenerationMouse2019[]24
miR-21Upregulates cyclin-D1 and accelerates the G1/S phase transition of hepatocytesMouse2016[]25
miR-10aDownregulates the EphA4 to increase the percentage of S phase and G2/M phase cellsRat2018[]26
ExosomeHepatocyte-derived exosome can directly fuse with the hepatocytes, transfer neutral ceramidase and SK2, and promote SLP synthesis to enhance LRMouse2016[]27
Nrf2ROS 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 PHMouse2015[]28
Nrf2 is also involved in HPC-mediated LR under a chronic liver disease backgroundMouse2019[]29
Baicalin induces Nrf2 accumulation in cytoplasm leads to NLRP3 inflammasome activation and increases expression of IL-18, which induces hepatocytes proliferationMouse2020[]30
NegativeNrf2Excessive activation of Nrf2 can delay proliferation and induce apoptosis of hepatocytes in the regenerating liver through targeting p15 and Bcl2l11 genesMouse2014[]31
Tmub1Interacts with cyclin A2 during the cell cycle, and the overexpression of Tmub1 may postpone cyclin A2 and cyclin B1 degradation in the M phaseRat2018[]32
Tmub1 can be downregulated by miR-27a/b to regulate hepatocyte proliferationRatHuman cell line2018[]33
Tmub1 negatively regulates liver regeneration by inhibiting STAT3 phosphorylationMouseHuman cell line2019[]34
PTENMyeloid 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 LRMouse2017[]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 regenerationMouse2017[]36
ALR can induce miR-26a expression to downregulate PTEN, and promote hepatocyte proliferation through the P-AKT/cyclin D1 pathwayRatHuman cell linePatient sample2019[]37
miR-34aTargets the Notch receptor, Bcl-2, and Bcl-xL, arrests cell cycle mainly in the G2/M phase, and increases cell apoptosis rateMouse2017[]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.

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750