Brain-derived neurotrophic factor induces angiogenin secretion and nuclear translocation in human umbilical vein endothelial cells

Abstract

Brain-derived neurotrophic factor (BDNF) is a well-known humoral protein that induces growth of neurons. Recent studies have suggested that BDNF could act as an angiogenesis inducer similar to vascular endothelial growth factor (VEGF). Angiogenin is a strong mediator of angiogenesis. It has particular characteristics both as a secreted protein and a transcription factor. After being incorporated into the cytoplasm, angiogenin is immediately transferred to the nucleus and then mediates the angiogenic effects of angiogenesis inducers, including VEGF. The aim of this study is to determine the association between BDNF and angiogenin. At first, we determined the secretion of angiogenin from human umbilical vein endothelial cells (HUVEC) induced by BDNF with enzyme-linked immunosorbent assay. Next, we determined BDNF-induced nuclear translocation of angiogenin by immunofluorescent staining. In addition, we examined the mRNA expression of angiogenin in HUVEC before and after BDNF stimulation by quantitative reverse transcriptase-polymerase chain reaction. As a result, we noted that BDNF induced angiogenin secretion and nuclear translocation without an increase in the mRNA expression in HUVEC. Furthermore, we demonstrated that BDNF-induced HUVEC proliferation was significantly suppressed when neomycin, a specific inhibitor of nuclear translocation of angiogenin, was administered. These findings indicate that nuclear translocation of angiogenin is critically involved in BDNF-induced proliferation of HUVEC. In conclusion, angiogenin contributes to angiogenesis induced by BDNF.

The secretion of the angiogenic and neurotrophic factor angiogenin is COPII and microtubule dependent

“…increased secretion without upregulation of expression) has been shown to occur in response to a variety of signals. Bone derived neurotrophic factor (BDNF) increases ANG secretion from vascular endothelial cells [47] and a wide range of signals can lead to increased ANG secretion from Mast cells. These include lipopolysaccharides, nerve growth factor and peptidoglycans [48].…”

PPAR-γ Mediates Ta-VNS-Induced Angiogenesis and Subsequent Functional Recovery after Experimental Stroke in Rats

“…In addition to VEGF, BDNF, as a novel angiogenic growth factor, plays a critical role in angiogenesis [32]. In one study, BDNF could act as a key inducer of angiogenesis and boost the proliferation of human umbilical vein ECs [33]. In a second study, downregulation of BDNF expression could impair the connections and survival of ECs [34].…”

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“…NTs can also induce angiogenesis by stimulating and regulating the expression of angiogenic factor as vascular endothelial growth factor (VEGF) [ 40 ]. BDNF induces in the HUVEC the secretion of angiogenin a potent angiogenic factor able also to increase wound healing [ 41 , 42 , 43 ]. Therefore, a dynamic relationship between vascular and neuronal tissues exists: HUVECs secrete NTs, which in turn drive and enhance axonal growth in the peripheral nerve [ 44 ].…”