Angiogenesis is crucial for liver regeneration after partial hepatectomy
| Autor: | Yugo Uda, Jiro Fujimoto, Junichi Yamanaka, Yuji Iimuro, Tadamichi Hirano, Shigeki Arii, Gakuhei Son, Akira Mori, Naoki Uyama |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology medicine.medical_specialty Angiogenesis medicine.medical_treatment Genetic Vectors Neovascularization Physiologic Biology Real-Time Polymerase Chain Reaction Adenoviridae Mice chemistry.chemical_compound Growth factor receptor Angiopoietin-1 medicine Animals Hepatectomy Cell Proliferation Vascular Endothelial Growth Factor Receptor-1 Hepatocyte Growth Factor Regeneration (biology) Endothelial Cells Receptor TIE-1 Ribonuclease Pancreatic Immunohistochemistry Receptor TIE-2 Liver regeneration Liver Regeneration Angiogenesis inhibitor Mice Inbred C57BL Vascular endothelial growth factor Liver chemistry Cancer research Surgery Hepatocyte growth factor Biomarkers medicine.drug |
| Zdroj: | Surgery. 153:70-77 |
| ISSN: | 0039-6060 |
| DOI: | 10.1016/j.surg.2012.06.021 |
| Popis: | Background Recent studies of hepatic regeneration have mainly focused on the growth of parenchymal cells. However, remodeling of liver vessels seems to be crucial during hepatic regeneration. In this study, we investigated the influence of antiangiogenesis on hepatic regeneration using sFlt-1, a soluble receptor for vascular endothelial growth factor that acts as a dominant negative receptor, and the hepatocyte growth factor antagonist NK4. Methods A sFlt-1–expressing adenoviral vector, an NK4-expressing adenoviral vector, or both combined were infected into C57BL6 mice via the tail vein. A 70% partial hepatectomy was performed on all of the mice 48 hours after infection. The remnants of the liver were removed after the partial hepatectomy, and hepatic regeneration was assessed by measuring the remnant liver weight and hepatocyte mitosis, bromodeoxyuridine staining, immunohistochemical staining with anti–platelet endothelial cell adhesion molecule-1 antibodies, and real-time polymerase chain reaction studies for angiogenic factors. Results The immunohistochemical staining for CD31 showed suppression of sinusoidal endothelial cells growth in sFlt-1–expressing adenoviral vector–and NK4-expressing adenoviral vector–infected mice. Increases in the remnant hepatic weight were significantly lower in the sFlt-1–expressing adenoviral vector–infected mice. The bromodeoxyuridine index and mitotic cell results revealed a significant decrease in hepatic regeneration in the sFlt-1–expressing adenoviral vector–and NK4-expressing adenoviral vector–infected mice. The suppressive effects on hepatic regeneration were significantly enhanced by combined sFlt-1–expressing adenoviral vector and NK4-expressing adenoviral vector infection. Real-time polymerase chain reaction results revealed the significant suppression of angiogenic growth factor receptors Tie-1 and Tie-2. Conclusion The angiogenesis inhibitor significantly suppressed hepatic regeneration. These results suggest that hepatic regeneration after hepatectomy closely correlates with angiogenesis. |
| Databáze: | OpenAIRE |
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