Expression of VEGFR-2 during Liver Regeneration after Partial Hepatectomy in a Bioluminescence Mouse Model

Abstract

Background: Liver regeneration requires the formation of new blood vessels. Endothelial cell proliferation is stimulated by vascular endothelial growth factor (VEGF) and its receptor tyrosine kinase VEGFR-2. The aim of this study was to investigate VEGFR-2 expression in vivo during liver regeneration after partial hepatectomy (PHx). Methods: Transgenic VEGFR-2-luc mice were used in which the luciferase reporter gene was under control of the VEGFR-2 promoter. Following 2/3 PHx, the mice underwent in vivo bioluminescence imaging until the 14th postoperative day. Additionally, liver tissue was analyzed by immunohistochemistry, in vitro luminescence assays, and quantitative RT-PCR. Results: In vivo bioluminescence imaging showed a significant increase in VEGFR-2 promoter activity after PHx. Maximum signal was recorded on the 3rd day; 8 days postoperatively the signal intensity decreased significantly. On the 14th day, bioluminescence signal reached almost baseline levels. Immunohistochemistry, quantitative RT-PCR, and in vitro luminescence confirmed a significant increase on the 3rd day following resection. The mRNA expression of VEGFR-2 was significantly higher on day 3 than preoperatively as well as on day 8. Conclusion: In vivo bioluminescence imaging with transgenic VEGFR-2-luc mice is feasible and provides a convenient model for noninvasively studying VEGFR-2 expression during liver regeneration. This may facilitate further experiments with modulation of angiogenesis by different substances.