Prometheus’ Challenge: Molecular, Cellular and Systemic Aspects of Liver Regeneration

Pahlavan, Payam S.; Feldmann, Robert; Zavos, Christos; Kountouras, Jannis

doi:10.1016/j.jss.2005.12.011

Cited by 75 publications

(64 citation statements)

References 152 publications

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“…Genes related to the initial phase of regeneration, such as TNF-a and IL-6, which prime hepatocytes into a state in which they are susceptible to growth factors [16,17] , were expressed at later time points in our model. Nonetheless, both cytokines were expressed at lower levels or were delayed after SH compared to PH.…”

Section: Discussionmentioning

confidence: 99%

“…Activation of NF-κB as well as expression of important cytokines and growth factors depend on the amount of resected liver tissue. The underlying mechanisms are not yet clear, although they may be associated with the liver's ability to regenerate and to reduce tissue to fit current requirements [16,28] .…”

Section: Discussionmentioning

confidence: 99%

“…This effect exceeds a linear size correlation, which led to the conclusion that graft or remnant liver size influences regeneration. The underlying molecular mechanisms, however, are not well understood [16][17][18][19] . In particular, the role of proregenerative cytokines (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration

Sowa¹,

Best²,

Benkő³

et al. 2008

WJG

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AIM:To investigate the molecular events involved in liver regeneration following subtotal hepatectomy (SH) as previous studies have largely focused on partial hepatectomy (PH). METHODS:Male Wistar rats were subjected to 70% PH or 90% SH, respectively, and sacrificed at different times after surgery. Untreated and sham-operated animals served as controls. Serum and liver samples were obtained to investigate liver function, apoptosis (TUNEL assay) and transcription factors (NF-κB, Stat3; ELISA) or cytokines (HGF, TNF-a, IL-6, TGF-a, TGF-b; quantitative RT-PCR) involved in liver regeneration. RESULTS:Serum levels of ALT and AST in animals with 70% PH differed significantly from sham-operated and control animals. We found that the peak concentration 12 h after surgery returned to control levels 7 d after surgery. LDH was increased only at 12 h after 70% PH compared to sham. Bilirubin showed no differences between the sham and 70% resection. After PH, early NF-κB activation was detected 12 h after surgery (313.21 ± 17.22 ng/mL), while there was no activation after SH (125.22 ± 44.36 ng/mL) compared to controls (111.43 ± 32.68 ng/mL) at this time point. In SH, however, NF-κB activation was delayed until 24 h (475.56 ± 144.29 ng/mL). Stat3 activation was similar in both groups. These findings correlated with suppressed and delayed induction of regenerative genes after SH (i.e. TNF-a 24 h postoperatively: 2375 ± 1220 in 70% and 88 ± 31 in 90%; IL-6 12 h postoperatively: 2547 ± 441 in 70% and 173 ± 82 in 90%). TUNEL staining revealed elevated apoptosis rates in SH (0.44% at 24 h; 0.63% at 7 d) compared to PH (0.27% at 24 h; 0.15% at 7 d). CONCLUSION:The molecular events involved in liver regeneration are significantly influenced by the extent of resection as SH leads to suppression and delay of liver regeneration compared to PH, which is associated with delayed activation of NF-κB and suppression of proregenerative cytokines.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration

Sowa¹,

Best²,

Benkő³

et al. 2008

WJG

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show abstract

“…Substances that can positively or negatively affect liver regeneration is one of the most attractive topics in modern science [35].…”

Section: Discussionmentioning

confidence: 99%

The Use of Erythropoietin in Liver Regeneration in Pigs after Partial Hepatectomy

Wiederkehr¹,

Carvalho²,

Wiederkehr³

et al. 2015

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A partial hepatectomy is a surgical procedure performed during the living-donor liver transplantation and sometimes the only option for patients with hepatocarcinoma. However the remnant liver after the hepatectomy is still a major concern. Therefore, the process of liver regeneration has been a constant theme of study in order to optimize this process. Erythropoietin, a hormone produced by the kidney and involved in protecting organs like heart, liver and kidney itself against injuries can be one of these factors that could accelerate the liver regeneration. This study aims to observe if erythropoietin can accelerate the process of liver regeneration after partial hepatectomy in pigs. Methods: 8 pigs were classified into 2 groups of 4 pigs each: the control group and the test group. The animals in the first group underwent an application of saline solution subcutaneous on the day before the hepatectomy. Instead of saline solution, the test groups received a subcutaneous injection of 200 UI/lg of recombinant erythropoietin also on the day before the surgical procedure. After 7 days since the hepatectomy, in each animal the liver was biopsied in two regions, one next to the hepatectomy section and other far from it. The liver regeneration was analyzed using Ki-67. Results: Pigs from control group presented the following results: Control pig I: 30% of regeneration in the hepatectomy section and 10% in the region far from it; control pig II 24% and 4%; control pig III 27% and 7%. The test group presented no significant liver regenera-* Corresponding author. H. A. Wiederkehr et al. 519tion since Ki-67 could not identify cell proliferation in neither the biopsied areas. Conclusion: Since the number of pigs was not statistically significant, we could not conclude any further hypothesis. We strong believe that enhancing the number of pigs and testing different doses, we will be able to reach further conclusions.

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“…The first signaling cascade regulates the cyclin D1/p21 and also protects against cell death, for example by up-regulating FLIP, Bcl2 and Bcl-xL. The latter pathway regulates cell size via mammalian target of rapamycin (mTOR) (Fausto, 2000;Serandour et al, 2005;Pahlavan et al, 2006;Fujiyoshi & Ozaki 2011). Numerous growth factors (for example HGF, TGF-α, EGF, glucagon, insulin and cytokines like TNF, IL-1 and -6 and somatostatin (SOM)) are implicated in the regeneration process.…”

Section: Hepatocyte and Regenerationmentioning

confidence: 99%

Hepatocytes and Progenitor - Stem Cells in Regeneration and Therapy

Amicone¹,

Citarella²,

Tripodi³

et al. 2012

Liver Regeneration

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Prometheus’ Challenge: Molecular, Cellular and Systemic Aspects of Liver Regeneration

Cited by 75 publications

References 152 publications

Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration

Extent of liver resection modulates the activation of transcription factors and the production of cytokines involved in liver regeneration

The Use of Erythropoietin in Liver Regeneration in Pigs after Partial Hepatectomy

Hepatocytes and Progenitor - Stem Cells in Regeneration and Therapy

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