Samples of blood and remnant liver tissue were obtained 24 hours after hepatectomy and the following parameters were evaluated: Biochemical analysis; liver regeneration rate; survival rate; and real-time polymerase chain reaction for interleukin-1 beta (Il1b), tumor necrosis factor alpha (Tnfa), matrix metalloproteinase (Mmp) 2 and Mmp9 mRNA.
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.
Stab2-iCre<sup>tg/wt</sup>;Hgf<sup>fl/fl</sup> (Hgf<sup>ΔLSEC</sup>) mice were generated to abrogate Hgf expression selectively in LSEC from early fetal development onwards, to study global development, metabolic and endothelial zonation, and organ functions as well as liver regeneration in response to 70% partial hepatectomy (PH).
Importantly, hepatectomy-induced hyperactivation of CyclinD1 and liver regeneration in CREBZF LKO mice was reversed by selective STAT3 inhibitor cucurbitacin I.
Whereas hepatocyte growth factor (HGF) and epidermal growth factor (EGF) are direct mitogens to hepatocytes, inflammatory cytokines such as TNFα and IL-6 also play essential roles in the liver regeneration process.
Whereas hepatocyte growth factor (HGF) and epidermal growth factor (EGF) are direct mitogens to hepatocytes, inflammatory cytokines such as TNFα and IL-6 also play essential roles in the liver regeneration process.
Transforming growth factor-β (TGF-β) and hepatocyte growth factor (HGF) are among the key signals involved in liver regeneration and as component of HPCs niche regulates HPCs biology.
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).
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.
Our data suggest that the degree of liver regeneration indicated by high levels of HGF within the liver is a dismissible factor in the post-KPE disease course.
Whereas hepatocyte growth factor (HGF) and epidermal growth factor (EGF) are direct mitogens to hepatocytes, inflammatory cytokines such as TNFα and IL-6 also play essential roles in the liver regeneration process.
Our results suggest that TAZ stimulates liver regeneration through IL-6-induced hepatocyte proliferation and inhibition of cell death after liver injury.-Kim, A. R., Park, J. I., Oh, H. T., Kim, K. M., Hwang, J.-H., Jeong, M. G., Kim, E.-H., Hwang, E. S., Hong, J.-H. TAZ stimulates liver regeneration through interleukin-6-induced hepatocyte proliferation and inhibition of cell death after liver injury.
Cytokines TNF-α, IL-6, IL-12, IL-1β, IL-8, IFN-γ and IL-2 were ameliorated by the SRBAL treatment, while levels of M-CSF; HGF, EGF and VEGF; IL-1RA and MIF rose on priming, proliferation and the late phase of liver regeneration.
Summarizing, data here reported demonstrate that inhibition of HO-1 enhances rat liver regeneration after PH which is associated to a very rapid increase in the levels of inflammatory mediators such as IL-6, phopsho-JNK and phospho-STAT3, suggesting that HO-1 could act as a negative modulator of liver regeneration.
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.
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.
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.
Mechanistically, CD169<sup>+</sup> cells contributed to liver regeneration by inducing hepatic interleukin-6 (IL-6) production and signal transducer and activator of transcription 3 activation.