Our results suggest that geraniol plays a significant role during liver regeneration, which involves the elevated expression of TNFα and IL6 48 h after PH.
ALR is regulated by Nrf2, acts as a liver regeneration and antioxidative protein and, therefore, links oxidative stress to hepatic regeneration to ensure survival of damaged cells.
An increased expression of genes associated with liver regeneration (STAT3, ALR) and energy metabolism (PGC-1α, COX, Nampt) was found in T2 (p < 0.05).
Also, albumin, proliferation activities and molecules associated with liver regeneration (e.g. interleukin-6, gp130, ATP binding cassette transporters, cyclin A) were more increased in hPE administration group than Non-hPE group. hPE administration suppressed activated T-cell proliferation via increasing anti-inflammatory cytokines and decreasing pro-inflammatory cytokines.
Hepatocyte growth factor/scatter factor (HGF/SF) stimulates hepatocyte DNA synthesis and protects against apoptosis; in vivo it promotes liver regeneration and reduces fibrosis.
Hepatocyte proliferation was also promoted in partial hepatectomized rats by hPH treatment. hPH increased liver regeneration rate, double nucleic cell ratio, mitotic cell ratio, proliferating cell nuclear antigen (PCNA), and K<sub>i</sub>-67 positive cells in vivo as well as interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and hepatocyte growth factor (HGF).
Liver regeneration in this model was severely impaired due to the shift from the activation of pro-regenerative IL-6/STAT3 to anti-regenerative IFN-γ/STAT1 pathway.
Importantly, although IL-6R deficient mice were strongly affected by PHX, survival and regeneration of IL-6 trans-signaling mice was indistinguishable from control mice, demonstrating that IL-6 trans-signaling fully compensates for disabled classic signaling in liver regeneration after PHX.
This review focuses on studies that present IL-6 as a key factor in regulating liver regeneration and in supporting effector immune functions and suggests that these functions of IL-6 can be exploited in treatment strategies for liver pathologies.
Accordingly, treatment of CD169<sup>+</sup> cell-depleted animals with IL-6/IL-6 receptor rescued liver regeneration and severe pathology following PHx.
In the liver, the signal and function of tumor necrosis factor-like weak inducer of apoptosis (TWEAK) have mainly been assessed in association with liver regeneration.
In addition, analysis of the liver specimens indicated that injection with the 1% pO<sub>2</sub> secretome maximized the expression of the intermediate molecules of the PIP3/Akt and IL-6/STAT3 signaling pathways, all of which are known to promote liver regeneration.
Stress-induced GCs hyper-secretion triggers glucocorticoid receptor (GR)-dependent transcriptional factor, nuclear factor kappa B (NFκB), which interferes TNFα-IL6 and keap1-Nrf2 pathways in liver regeneration and obesity through fine-tuning of TNFα, IL6 and Nrf2 signaling.
Therefore, HGF and SDF-1 may represent important chemoattractants for transplanted BMC in the injured liver, where these cells can give rise to populations of extrahepatic macrophages, neutrophils and endothelial progenitor cells that can interact synergistically with other liver cells towards the modulation of an anti-fibrotic cytokine profile promoting the onset of liver regeneration.
TNF-α, IL-6, HGF, TSP-1 and TGF-β1 were essential factors for the formation of tight junction and the establishment of hepatocytes polarity in liver regeneration.
The 90PH rats also showed delayed liver regeneration and the most severe liver injury, as reflected by increased serum ALT, AST and TBIL levels, hepatocellular vacuolization, and inflammatory and endothelial constriction gene expressions (TNF-α, IL-1β, MIP-1α, ET-1 and TM-1).
Augmenter of liver regeneration (ALR) is a multifunctional mitochondrial protein that demonstrates anti-oxidative and anti-apoptotic properties and plays a key role in liver regeneration.