The vascular endothelial growth factor signaling pathway regulates liver sinusoidal endothelial cells during liver regeneration after partial hepatectomy
Abstract
Introduction Liver regeneration after partial hepatectomy is a very complex and well-regulated procedure. It utilizes all liver cell types, which are associated with signaling pathways involving growth factors, cytokines, and stimulatory and inhibitory feedback of several growth-related signals. Liver sinusoidal endothelial cells (LSECs) contribute to liver regeneration after partial hepatectomy. Vascular endothelial growth factor (VEGF) has various functions in LSECs. In this review, we summarize the relationship between VEGF and LSECs involving VEGF regulatory activity in the vascular endothelium. Areas covered Maintenance of the fenestrated LSEC phenotype requires two VEGF pathways: VEGF stimulated-NO acting through the cGMP pathway and VEGF independent of nitric oxide (NO). The results suggest that VEGF is a key regenerating mediator of LSECs in the partial hepatectomy model. NO-independent pathway was also essential to the maintenance of the LSEC in liver regeneration. Expert opinion Liver regeneration remains a fascinating and significative research field in recent years. The liver involved of molecular pathways except for LSEC-VEGF pathways that make the field of liver further depth studies should be put into effect to elaborate the undetermined confusions, which will be better to understand liver regeneration.
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In response to reduced oxygen delivery, endothelial cells release VEGF and nitric oxide, which enhance nutrient and oxygen supply to the remaining liver tissue and support the initiation of regeneration.
“In response, these cells release VEGF and nitric oxide (NO)[25-27], which enhance nutrient and oxygen supply to the remaining liver tissue and support the initiation of the regeneration process.”
From Liver regeneration after partial hepatectomy: Triggers and mechanisms (2025) · cites this paper as [25]
Cites
Michalopoulos, G. K. (2007) · Journal of Cellular Physiology · doi:10.1002/jcp.21172 · Cited by 1,384 · see citing works
Liver sinusoidal endothelial cells in hepatic fibrosis
DeLeve, L. D. (2015) · Hepatology · doi:10.1002/hep.27376 · Cited by 482 · see citing works
IL‐6 Trans‐signaling Controls Liver Regeneration After Partial Hepatectomy
Fazel Modares, N., Polz, R., Haghighi, F., Lamertz, L., Behnke, K., Zhuang, Y., Kordes, C., Häussinger, D., Sorg, U. R., Pfeffer, K., et al. (2019) · Hepatology · doi:10.1002/hep.30774 · Cited by 113 · see citing works
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Liver regeneration after partial hepatectomy: Triggers and mechanisms
Korchilava, B., Khachidze, T., Megrelishvili, N., Svanadze, L., Kakabadze, M., Tsomaia, K., Jintcharadze, M., & Kordzaia, D. (2025) · World Journal of Hepatology · doi:10.4254/wjh.v17.i7.107378 · Cited by 21 · see citing works
Li, L., Wu, Q., Lin, Z., Liang, S., Fu, Q., Wei, Y., Wang, B., & Su, T. (2026) · Radiotherapy and Oncology · doi:10.1016/j.radonc.2025.111225 · Cited by 1 · see citing works
Self-citation
- Authors
- Lu, J., Zhao, Y.-L., Zhang, X.-Q., & Li, L.-J.
- Affiliations
- State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital of Medicine School, Zhejiang University, Hangzhou, China
- Venue
- Expert Review of Gastroenterology & Hepatology
- Publisher
- Informa UK Limited
- Published
- 2020-10-14
- Volume
- 15
- Issue
- 2
- Pages
- 139-147
- ISSN
- 1747-4124 (ISSN-L)
- 1747-4132
- OpenAlex
- W3084003309
- Cited by
- 22
- References
- 3
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 5 · 2022: 4 · 2021: 3 · 2020: 1
- FWCI
- 0.43
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Expert Review of Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- provincial nature and science fund (LQ20H030012)
- 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 › Organ Transplantation Techniques and Outcomes
- Keywords
- vascular endothelial growth factor, liver sinusoidal endothelial cells, liver regeneration, partial hepatectomy, nitric oxide, cGMP signaling, endothelial signaling
- MeSH terms
- Animals, Hepatectomy, Humans, Liver Regeneration, Phenotype, Signal Transduction, Hepatocytes, Vascular Endothelial Growth Factors, Endothelial Cells, Cell Proliferation
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