Effect of vascular endothelial growth factor on functional recovery after hepatectomy in lean and obese mice

Redaelli, C.; Semela, David; Carrick, Francine E.; Ledermann, M.; Candinas, Daniel; Sauter, Bernhard; Dufour, Jean–François

doi:10.1016/j.jhep.2003.10.027

Cited by 58 publications

(45 citation statements)

References 32 publications

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“…57 Our data, agree with other studies which found that hepatic expression of FLT1 mRNA was decreased in obese mice compared with lean mice and suggest a potential involvement of vascular endothelial growth factor and its receptor in the pathogenesis of NAFLD. 58 In a general view, it is recognized that protein expression is directly correlated to the expression of its cognate mRNA, which in turn generally is inversely correlated to the expression of its regulatory miRNA(s). Our data demonstrated that this phenomenon is plausible to explain LITAF increase, PTEN and FLT1 decrease, in all hypercaloric regimens.…”

Section: Discussionmentioning

confidence: 99%

Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease

Alisi

Sacco

Bruscalupi

et al. 2011

Laboratory Investigation

178

116

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Nonalcoholic fatty liver disease (NAFLD) is an emerging disease with a broad spectrum of liver conditions. The complex molecular pathogenesis of NAFLD is still unclear. In this study, we conducted an analysis of microRNA (miRNA) expression profiles in liver of rats made NAFLD by different diets. To this aim, Sprague-Dawley rats were fed ad libitum for 3 months with different diets: standard diet (SD), diet enriched in fats and low in carbohydrates (HFD), SD with high fructose (SD-HF) and diet with high levels of fats and fructose (HFD-HF). Our results demonstrated that the treatment with different dietetic regimens caused a significant increase of the body weight and the alteration of some metabolic parameters compared with control animals, as well as various liver injuries. The miRNAs analysis showed the significant downregulation of three miRNAs (miR-122, miR-451 and miR-27) and the upregulation of miR-200a, miR-200b and miR-429 in HFD, SD-HF and HFD-HF rats. Besides, miR-21 expression was significantly decreased only in fructose-enriched diets. These miRNAs target molecules involved in the control of lipid and carbohydrate metabolism, signal transduction, cytokine and chemokine-mediated signaling pathway and apoptosis. Western blot analysis of PKCd, LITAF, ALDOLASE-A, p38MAPK, PTEN, LIPIN1, EPHRIN-A1, EPHA2 and FLT1 showed a diet-induced deregulation of all these proteins. Interestingly, the expression pattern of LITAF, PTEN, LIPIN1, EPHRIN-A1, EPHA2 and FLT1 might be well explained by the trend of their specific mRNAs, by potentially regulatory miRNAs, or both. In conclusion, we highlight for the first time the potential involvement of novel determinants (miRNAs and proteins) in the molecular pathogenesis of diet-induced NAFLD.

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Section: Discussionmentioning

confidence: 99%

Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease

Alisi

Sacco

Bruscalupi

et al. 2011

Laboratory Investigation

178

116

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“…To determine whether increased VEGF-A secretion by tumor cells would lead to an increase in the contribution of bone marrow-derived endothelial progenitors to the tumor vasculature, B6RV2 cells were transduced with a retroviral vector encoding the human VEGF-A 165 cDNA (MSCVneo-VEGF-A 165 ). Human VEGF-A has previously been shown to be biologically active in mice (27,28). Tumor cells were implanted s.c. in mice transplanted with GFP ϩ marrow; after 10 days, they were harvested, cryosectioned, and stained with CD31 and VE-cadherin, and GFP ϩ endothelial cells incorporating into tumor vasculature were quantified.…”

Section: Vegf-a Is a Potent Inducer Of Both Angiogenesis And Vasculogmentioning

confidence: 99%

Minimal Contribution of Marrow-Derived Endothelial Precursors to Tumor Vasculature

Larrivée

Niessen²,

Pollet³

et al. 2005

The Journal of Immunology

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During embryogenesis, vascular and hemopoietic cells originate from a common precursor, the hemangioblast. Recent evidence suggests the existence of endothelial precursors in adult bone marrow cells, but it is unclear whether those precursors have a role in tumor neovascularization. In this report, we demonstrate that murine bone marrow contains endothelial progenitors, which arise from a cell with self-renewing capacity, and can integrate into tumor microvasculature, albeit at a very low frequency. A transgenic double-reporter strategy allowed us to demonstrate definitively that tumor bone marrow-derived endothelial cells arise by transdifferentiation of marrow progenitors rather than by cell fusion. Single cell transplants showed that a common precursor contributes to both the hemopoietic and endothelial lineages, thus demonstrating the presence of an adult hemangioblast. Furthermore, we demonstrate that increased vascular endothelial growth factor (VEGF)-A secretion by tumor cells, as well as activation of VEGF receptor-2 in bone marrow cells does not alter the mobilization and incorporation of marrow-derived endothelial progenitors into tumor vasculature. Finally, in human umbilical cord blood cells, we show that endothelial precursors make up only ∼1 in 107 mononuclear cells but are highly enriched in the CD133+ cell population. By ruling out cell fusion, we clearly demonstrate the existence of an adult hemangioblast, but the differentiation of marrow stem cells toward the endothelial lineage is an extremely rare event. Furthermore, we show that VEGF-A stimulation of hemopoietic cells does not significantly alter this process.

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“…2,4 Nevertheless, numerous groups 1,[8][9][10] conducting murine studies still use modifications of the technique originally described by Higgins and Anderson for rats, meaning the resection of the 2 left lateral lobes of the liver, thus mis takenly implying the same amount of resected tissue as in rats.…”

mentioning

confidence: 99%

Effect of different liver resection methods on liver damage and regeneration factors VEGF and FGF-2 in mice

et al. 2012

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Background: Different approaches to study liver regeneration in murine models have been proposed. We investigated the effect of different liver resection models on liver damage and regeneration parameters in mice. Methods:We compared the technical aspect of the 2 most commonly used techniques of 50% and 70% liver resection. Liver damage, as determined by the change in serum alanine aminotransferase and aspartate aminotransferase, as well as the regeneration parameters VEGF and FGF-2 were analyzed at 6 time points. A postoperative vitality score was introduced.Results: Cholestasis was not observed for either technique. Both resection techniques resulted in full weight recovery of the liver after 240 hours, with no significant difference between sham and resection groups. Postoperative animal morbidity and total protein levels did not differ significantly for either method, indicating early and full functional recovery. However, comparing the mitogenic growth factors FGF-2 and VEGF, a significant increase in serum levels and, therefore, increased growth stimulus, was shown in the extended resection group. Conclusion:Extended resection led to a greater response in growth factor expression. This finding is important since it shows that growth factor response differs acdording to the extent of resection. We have demonstrated the need to standardize murine hepatic resection models to adequately compare the resulting liver damage.Contexte : Différentes approches ont été proposées pour étudier la régénérescence du foie dans des modèles murins. Nous avons exploré l'effet de divers modèles de résection sur l'atteinte hépatique et les paramètres de la régénérescence chez la souris. Méthodes :Nous avons comparé l'aspect technique des 2 approches les plus couramment utilisées, soit les résections de 50 % et de 70 % du foie. L'atteinte hépatique, déter-minée en fonction de la modification des taux d'alanine aminotransférase et d'aspartate aminotransférase sériques, ainsi que les paramètres de régénérescence VEGF (facteur de croissance endothéliale vasculaire) et FGF-2 (facteur de croissance des fibroblastes) ont été analysés à 6 moments. Un score de vitalité postopératoire a en outre été introduit.

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Effect of vascular endothelial growth factor on functional recovery after hepatectomy in lean and obese mice

Cited by 58 publications

References 32 publications

Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease

Mirnome analysis reveals novel molecular determinants in the pathogenesis of diet-induced nonalcoholic fatty liver disease

Minimal Contribution of Marrow-Derived Endothelial Precursors to Tumor Vasculature

Effect of different liver resection methods on liver damage and regeneration factors VEGF and FGF-2 in mice

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