The potential role of brain-derived neurotrophic factor (BDNF) in angiogenesis

Abstract

Background and Aim: Hepatocellular carcinoma is a hypervascularized solid tumor, in which angiogenesis plays an essential role. The present study aims to investigate the potential role of brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, in the angiogenic behavior of endothelial cells. Materials and Methods: One normal mouse endothelial cell line and one tumor-derived endothelial cell line were used in an in vitro setting. These two cell lines were treated with recombinant BDNF protein, TrkB blocker-K252a or in combination. In addition, BDNF level was up-regulated in the normal endothelial cells by transfection. The viability of cells was determined by MTT assay, and the percentage of apoptotic cells was quantified by Annexin V labeling. Cell motility was assessed by cell migration assay. The expression of BDNF, HIF-1α, and VEGF was detected by semi-quantitative RT-PCR and Western blot. Results: Firstly, the two cell lines expressed different levels of endogenous BDNF. The tumor-derived endothelial cells with a higher level of endogenous BDNF, demonstrated a higher proliferation rate than that in the normal endothelial cells, which had a lower endogenous BDNF level. Secondly, exogenous BDNF administration could promote cell proliferation in both cell lines. Thirdly, exogenous BDNF up-regulated the expression of HIF-1α and VEGF in the tumor-derived endothelial cells, and augmented the expression of BDNF and VEGF in the normal endothelial cells. Lastly, up-regulation of BDNF by transfection promoted cell migration and abrogated serum-starvation induced apoptosis. Conclusion: The present study suggested the potential role of BDNF in physiological and pathological angiogenesis.