The role of yeast-derived β-glucan in angiogenesis has not been elucidated because there have been few specific studies on its clinical and physiological significance. Therefore, this study investigated the correlation between β-glucan and histone deacetylase 5 (HDAC5) in human umbilical vein endothelial cells (HUVECs), revealing the role of β-glucan in angiogenesis. We confirmed that HDAC5 was phosphorylated by β-glucan stimulation and released from the nucleus to the cytoplasm. Furthermore, we found that β-glucan-stimulated HDAC5 translocation mediates the transcriptional activation of MEF2. As a result, the expression of KLF2, EGR2, and NR4A2, whose expression is MEF2-dependent and involved in angiogenesis, increased. Thus, we showed the activity of β-glucan in angiogenesis through in vitro and ex vivo assays including cell migration, tube formation, and aortic ring analyses. Specifically, application of an HDAC5 inhibitor repressed MEF2 transcriptional activation in both in vitro and ex vivo angiogenesis. HDAC5 inhibitor LMK235 inhibited the proangiogenic activity of beta-glucan, suggesting that β-glucan induces angiogenesis through HDAC5. These findings suggest that HDAC5 is essential for angiogenesis, and that β-glucan induces angiogenesis. In conclusion, this study demonstrates that β-glucan induces angiogenesis through HDAC5. It also suggests that β-glucan has potential value as a novel therapeutic agent for modulating angiogenesis.
Keywords: Angiogenesis; Beta-glucan; Endothelial cell; Histone deacetylase 5; MEF2.
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