Angiogenesis is crucial for liver regeneration after partial hepatectomy
Open accessAbstract
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.
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Increased portal pressure and blood flow enhance shear stress effects and promote the release of growth factors, which play a critical role in hepatocyte proliferation and angiogenesis.
“This enhances shear stress effects and promotes the release of growth factors, which play a critical role in hepatocyte proliferation and angiogenesis[44].”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [44]
The introductory passages (indexed as Abstract; page unavailable) say that growth factors stimulate hepatocytes and that VEGF expression increases after partial hepatectomy. The Discussion links angiogenic signaling to liver regeneration. The paper does not say that increased portal pressure or blood flow creates shear stress that promotes growth-factor release; searches for those terms found no supporting passage. (LLM, conf=0.86)
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- Authors
- Uda, Y., Hirano, T., Son, G., Iimuro, Y., Uyama, N., Yamanaka, J., Mori, A., Arii, S., & Fujimoto, J.
- Affiliations
- Hyogo Medical University (JP)
- Asahi University Hospital (JP)
- Tokyo Medical and Dental University (JP)
- Corresponding author
- Fujimoto, Jiro
- ORCID
- Fujimoto, Jiro
- Venue
- Surgery
- Publisher
- Elsevier BV
- Published
- 2013-01
- Volume
- 153
- Issue
- 1
- Pages
- 70-77
- ISSN
- 0039-6060 (ISSN-L)
- OpenAlex
- W2143373628
- Cited by
- 41
- References
- 30
- Citations by year
- 2025: 3 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 6 · 2018: 2 · 2017: 2 · 2016: 4 · 2015: 3 · 2014: 4 · 2013: 2
- FWCI
- 1.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Surgery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science
- Ministerio de Sanidad, Consumo y Bienestar Social
- Topics
- Health Sciences › Medicine › Hepatology › Liver physiology and pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Keywords
- angiogenesis, liver regeneration, partial hepatectomy, soluble fms-like tyrosine kinase-1, NK4, anti-angiogenic therapy, vascular endothelial growth factor, Tie1, Tie2, sinusoidal endothelial cells, hepatocyte proliferation, adenoviral gene transfer
- MeSH terms
- Adenoviridae, Animals, Genetic Vectors, Hepatectomy, Immunohistochemistry, Liver, Liver Regeneration, Male, Mice, Inbred C57BL, Ribonuclease, Pancreatic, Biomarkers, Hepatocyte Growth Factor, Neovascularization, Physiologic, Vascular Endothelial Growth Factor Receptor-1, Angiopoietin-1, Endothelial Cells, Receptor, TIE-2, Receptor, TIE-1, Cell Proliferation, Mice, Real-Time Polymerase Chain Reaction
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