VEGF is Important for Early Liver Regeneration After Partial Hepatectomy

Bockhorn, Maximilian; Goralski, Michal; Prokofiev, Dennis; Dammann, Philipp; Grunewald, P; Trippler, Martin; Biglarnia, Ali-Reza; Kamler, Markus; Niehues, E.; Frilling, A.; Broelsch, Christoph E.; Schlaak, Joerg F.

doi:10.1016/j.jss.2006.07.027

Cited by 106 publications

(90 citation statements)

References 26 publications

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“…Therefore, very stringent criteria have to be fulfilled prior to hepatectomy to ensure donor safety [9][10][11] . For the donor, fast liver regeneration is imperative to reduce the probability of liver insufficiency [12,13] . Thus, an improvement in regenerative capacity would enhance donor safety and increase the possibility of including individuals who are not eligible for donation due to insufficient liver size [8,14] .…”

Section: Introductionmentioning

confidence: 99%

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: Introductionmentioning

confidence: 99%

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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“…A critical component of the liver regeneration response is thought to be dependent on angiogenesis since expansion of avascular islands of hepatocytes is associated with an angiogenic switch (1,2,37); however, the overall requirement of angiogenesis for liver regeneration is not fully defined. Thus partial hepatectomy is a compelling model in which to ascertain angiogenic cross talk in vivo, especially because of the well-defined timeline of molecular and cellular events that occur in the first several days in response to 70% hepatic resection (14,30,39).…”

mentioning

confidence: 99%

Inhibition of VEGF- and NO-dependent angiogenesis does not impair liver regeneration

Shergill

Das

Langer

et al. 2010

American Journal of Physiology-Regulatory, Integrative and Comp

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Angiogenesis occurs through a convergence of diverse signaling mechanisms with prominent pathways that include autocrine effects of endothelial nitric oxide (NO) synthase (eNOS)-derived NO and vascular endothelial growth factor (VEGF). However, the redundant and distinct roles of NO and VEGF in angiogenesis remain incompletely defined. Here, we use the partial hepatectomy model in mice genetically deficient in eNOS to ascertain the influence of eNOS-derived NO on the angiogenesis that accompanies liver regeneration. While sinusoidal endothelial cell (SEC) eNOS promotes angiogenesis in vitro, surprisingly the absence of eNOS did not influence the angiogenesis that occurs after partial hepatectomy in vivo. While this observation could not be attributed to induction of alternate NOS isoforms, it was associated with induction of VEGF signaling as evidenced by enhanced levels of VEGF ligand in regenerating livers from mice genetically deficient in eNOS. However, surprisingly, mice that were genetically heterozygous for deficiency in the VEGF receptor, fetal liver kinase-1, also maintained unimpaired capacity for liver regeneration. In summary, inhibition of VEGF- and NO-dependent angiogenesis does not impair liver regeneration, indicating signaling redundancies that allow liver regeneration to continue in the absence of this canonical vascular pathway.

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“…Upon early liver regeneration, VEGF has a key role in mediating angiogenetic gene expression and modulating microvasculature [6]. In addition, VEGF regulates the recruitment of rat liver progenitor sinusoidal endothelial cells to the liver, which is a crucial step for regeneration [29].…”

Section: Discussionmentioning

confidence: 99%

LYVE1 and PROX1 in the reconstruction of hepatic sinusoids after partial hepatectomy in mice

Meng¹

2017

Folia Morphol

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VEGF is Important for Early Liver Regeneration After Partial Hepatectomy

Cited by 106 publications

References 26 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

Inhibition of VEGF- and NO-dependent angiogenesis does not impair liver regeneration

LYVE1 and PROX1 in the reconstruction of hepatic sinusoids after partial hepatectomy in mice

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