효모 유래 글루칸에 의한 HDAC5 유도 혈관신생성 활성화 연구

Abstract

β-glucan is a polysaccharide found in large amounts in of bacteria, fungi, and yeast cell walls. The biological and physiological effects of β-glucan have been reported as anti-tumor, anti-diabetic, lowering cholesterol levels, and immunity enhancement. However, the role of yeast-derived β-glucan on angiogenesis has not been elucidated. There have been few specific studies on the clinical and physiological significance of yeast-derived β-glucan. Therefore, this study showed the correlation between β-glucan and histone deacetylase5 (HDAC5) in human umbilical vein endothelial cells (HUVECs), revealing the role of β-glucan on the activity of angiogenesis. We confirmed that HDAC5 was phosphorylated by β-glucan stimulation and released from the nucleus to the cytoplasm. In this study, we found that β-glucan-stimulated HDAC5 mediates the transcriptional activation of MEF2. As a result, the expression of KLF2, EGR2, and NR4A2 genes that are dependent on MEF2 and involved in angiogenesis increased. Thus, we showed the angiogenesis activity of β-glucan through cell migration, tube formation, and aortic ring analysis as in vitro and ex vivo angiogenesis assays. Specifically, inhibition of HDAC5 by an HDAC5 inhibitor repressed transcriptional activation of MEF2, in vitro and ex vivo angiogenesis. However, it was shown that β-glucan treatment restored MEF2 transcriptional activation, which had been inhibited. These findings suggest that HDAC5 is essential for angiogenesis and that β-glucan induces angiogenesis activity. In conclusion, this study demonstrates that β-glucan induces the activity of angiogenesis through HDAC5. It also suggests that β-glucan has potential value as a novel therapeutic agent modulating angiogenesis.